Key points
- Lymphoma is a cancer of lymphocytes and is divided into two large groups, Hodgkin and non-Hodgkin; there are dozens of subtypes with different behavior and treatment [1].
- A definitive diagnosis is possible only with a tissue biopsy, and staging is based on the Lugano criteria using PET-CT [2, 3].
- In advanced Hodgkin lymphoma, the nivolumab + AVD (N-AVD) regimen improved progression-free survival compared with brentuximab vedotin + AVD, and in the EHA guideline it is the preferred approach for patients over 60 years and a valid alternative in younger patients; PET-guided ABVD is also a proven option [5, 13, 25].
- In diffuse large B-cell lymphoma (DLBCL), the R-CHOP regimen is the standard first-line treatment [6, 24]; the newer Pola-R-CHP regimen slightly improved progression-free survival in patients at intermediate or high risk, with no significant difference in overall survival [7].
- In relapsed DLBCL, salvage chemoimmunotherapy and autologous stem cell transplantation is the standard treatment for eligible patients [23, 24, 31]; in early relapse (less than 12 months after first-line treatment), CAR T-cell therapy has been superior to this approach in trials [8, 9, 19].
- In follicular lymphoma and mantle cell lymphoma, combinations based on rituximab, bendamustine, lenalidomide and ibrutinib are the backbone of treatment [16, 26, 28, 29]; bispecific antibodies such as glofitamab, epcoritamab and mosunetuzumab are newer options for multiple relapses [10, 11, 12].
What is lymphoma?
Lymphoma is a cancer that arises from lymphocytes, the white blood cells of the immune system. These cells are found in the lymph nodes, spleen, bone marrow and many other tissues, so lymphoma can develop almost anywhere in the body; its most common sign, however, is painless enlargement of the lymph nodes.
The World Health Organization classification (fifth edition) divides lymphomas according to cell type (B, T or NK), microscopic appearance, surface markers and genetic features [1]. To compare lymphoma with other blood cancers, see the blood cancers page.
| Type | Behavior | Features | Main treatment |
|---|---|---|---|
| Classic Hodgkin lymphoma | Aggressive but highly treatable | Reed–Sternberg cells; common in young people | N-AVD or PET-guided ABVD; other options: BrECADD and BV-AVD [4, 5, 13, 18, 25] |
| Diffuse large B-cell lymphoma (DLBCL) | Aggressive | The most common aggressive non-Hodgkin lymphoma [1] | R-CHOP; newer option: Pola-R-CHP [6, 7, 24] |
| Follicular lymphoma | Slow-growing (indolent) | Long course with periods of relapse and remission | Active surveillance or rituximab-based immunochemotherapy, such as bendamustine-rituximab [14, 26] |
| Mantle cell lymphoma | Usually aggressive | Cyclin D1 expression | Immunochemotherapy plus ibrutinib [16, 29] |
| Marginal zone lymphoma (MZL) | Slow-growing | Extranodal (MALT), splenic and nodal types | Depends on the site; treatment of Helicobacter pylori infection in gastric MALT lymphoma [17, 22] |
T-cell lymphomas are also an important group, but they are not covered in detail on this page.
Signs and symptoms
- Painless enlargement of lymph nodes in the neck, armpit or groin that does not go away within a few weeks
- Cough, shortness of breath or a feeling of pressure in the chest (involvement of the mediastinal lymph nodes)
- Abdominal pain or a feeling of fullness due to an enlarged spleen or enlarged abdominal lymph nodes
- Fatigue, itchy skin and frequent infections
B symptoms
Three general symptoms known as “B symptoms” are unexplained fever, drenching night sweats and unexplained weight loss. Under the Lugano criteria, the suffix A or B (absence or presence of these symptoms) is reported only in the staging of Hodgkin lymphoma, but these symptoms are clinically important in all types of lymphoma [2].
Warning signs
Most enlarged lymph nodes are caused by simple infections and shrink within a few weeks. But in these cases a lymph node should be checked by a doctor:
- A lymph node that is painless, firm or getting bigger, or that lasts longer than a few weeks
- An enlarged lymph node together with unexplained fever, night sweats or weight loss
During treatment, report any fever to your care team right away; after CAR T-cell therapy, fever, low blood pressure or confusion needs prompt treatment [8].
Risk factors
- Immune deficiency or dysregulation (such as HIV infection, or immunosuppressive drugs after an organ transplant); the new World Health Organization classification places these lymphomas in a separate group [1].
- Infections: Epstein–Barr virus (EBV) is associated with some lymphomas [1], and chronic Helicobacter pylori infection is linked to gastric MALT lymphoma [17].
- Autoimmune diseases and chronic inflammation, which are particularly associated with marginal zone lymphoma [17].
- Older age, for most non-Hodgkin lymphomas, whereas Hodgkin lymphoma is also common in young people (the median age of patients in the HD21 trial was 31 years) [18].
Diagnosis and staging
Diagnostic pathway for lymphoma
- 1
Lymph node biopsy
Lymphoma can be diagnosed only by examining tissue. The best sample is the removal of an entire lymph node (excisional biopsy) or a core needle biopsy; fine-needle aspiration is usually not sufficient for diagnosis and subtyping [2].
- 2
Pathology, immunohistochemistry and genetic testing
The exact type of lymphoma is determined with specific stains (such as CD20, CD30 and cyclin D1), flow cytometry and, when needed, genetic tests [1].
- 3
- 4
Additional tests
Blood counts, liver and kidney tests, LDH, and testing for hepatitis B and HIV. A bone marrow biopsy is no longer routinely needed for staging Hodgkin lymphoma and most cases of DLBCL [2].
| Stage | Brief definition | Treatment group |
|---|---|---|
| I | Involvement of one lymph node or one group of adjacent lymph nodes | Limited |
| II | Two or more lymph node groups on the same side of the diaphragm | Limited (bulky stage II may be considered advanced, depending on the type of lymphoma) |
| III | Lymph nodes involved on both sides of the diaphragm, or nodes above the diaphragm together with the spleen | Advanced |
| IV | Disseminated extralymphatic involvement (such as the liver, lung or bone marrow) | Advanced |
Under the Lugano criteria, treatment decisions are usually based on dividing patients into limited disease (non-bulky stages I and II) and advanced disease (stages III and IV) [2].
Hodgkin lymphoma
Treatment regimens and doses: index24 regimens
Hodgkin lymphoma is one of the most treatable cancers. The classic ABVD regimen (doxorubicin, bleomycin, vinblastine and dacarbazine) was the standard for many years, and today the intensity of treatment is adjusted according to the response on interim PET-CT [13, 25].
In limited-stage disease, two to four cycles of chemotherapy are used, with or without radiotherapy, and the intensity of treatment depends on the patient’s risk group [25]. At relapse, salvage therapy containing an immune checkpoint inhibitor, followed by high-dose chemotherapy and autologous stem cell transplantation, is recommended for eligible patients [25]; in patients who have relapsed after transplantation or are not transplant candidates, pembrolizumab controlled the disease for longer than brentuximab vedotin [33].
Treatment of advanced Hodgkin lymphoma
Nivolumab + AVD
In the large S1826 trial in stages III and IV, adding the immunotherapy drug nivolumab to AVD controlled the disease better than BV-AVD, with few immune-related side effects [5]. The EHA guideline (2026) considers six cycles of N-AVD the preferred approach for patients over 60 years and a less intensive alternative to BrECADD for younger patients [25].
PET-guided ABVD
Two cycles of ABVD followed, if PET is negative, by four cycles of AVD without bleomycin; omitting bleomycin reduced lung toxicity without a significant loss of efficacy [13]. If interim PET is positive, treatment is switched to an escalated BEACOPP-based regimen. The EHA guideline considers this approach one of the options for younger patients [25].
PET-guided BrECADD
Bleomycin (ABVD and eBEACOPP): the risk of pulmonary toxicity increases with older age and chest radiotherapy [13].
Brentuximab vedotin (BrECADD and BV-AVD): blood counts before each dose; for peripheral neuropathy, reduce the dose or discontinue according to the label table; do not use with creatinine clearance below 30 mL/min or with moderate or severe hepatic impairment, and reduce the dose in mild hepatic impairment; concomitant use with bleomycin is contraindicated because of pulmonary toxicity [34].
For physicians
Treatment regimens and dosing: Hodgkin lymphoma
N-AVD (nivolumab + AVD; S1826 trial)
Newly diagnosed advanced-stage (stage III–IV) classic Hodgkin lymphoma, age 12 years and older; in the EHA guideline (2026), the preferred approach for patients over 60 years and a less intensive alternative to BrECADD in younger patients (level 1A)Cycle length: Every 28 days
Newly diagnosed advanced-stage (stage III–IV) classic Hodgkin lymphoma, age 12 years and older; in the EHA guideline (2026), the preferred approach for patients over 60 years and a less intensive alternative to BrECADD in younger patients (level 1A) [25]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nivolumab | Adults: 240 mg; under 18 years: 3 mg/kg (maximum 240 mg) | IV | Days 1 and 15 |
| Doxorubicin | 25 mg/m² | IV | Days 1 and 15 |
| Vinblastine | 6 mg/m² | IV | Days 1 and 15 |
| Dacarbazine | 375 mg/m² | IV | Days 1 and 15 |
Doses from the full text of the S1826 trial [5]. Prophylactic G-CSF was optional with N-AVD and mandatory with BV-AVD; dexrazoxane was permitted to reduce the risk of doxorubicin cardiotoxicity [5]. The cumulative doxorubicin dose over six cycles is 300 mg/m² [5]. In the EHA guideline (2026), N-AVD is recommended with PET-guided 30 Gy radiotherapy [25].
Evidence: SWOG S1826 (2024)
PET-guided ABVD (RATHL approach) and ABVD in limited-stage disease
Advanced classic Hodgkin lymphoma (interim PET-adapted approach); in limited stage: low-risk group, 2 cycles of ABVD followed by 20 Gy radiotherapy; in the less intensive approach for the high-risk group or patients over 60 years, 4 cycles of A(B)VD and 30 Gy radiotherapyCycle length: Every 28 days
Advanced classic Hodgkin lymphoma (interim PET-adapted approach); in limited stage: low-risk group, 2 cycles of ABVD followed by 20 Gy radiotherapy; in the less intensive approach for the high-risk group or patients over 60 years, 4 cycles of A(B)VD and 30 Gy radiotherapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Doxorubicin | 25 mg/m² | IV | Days 1 and 15 |
| Bleomycin | 10 units/m² | IV | Days 1 and 15 |
| Vinblastine | 6 mg/m² | IV | Days 1 and 15 |
| Dacarbazine | 375 mg/m² | IV | Days 1 and 15 |
Doses from the ClinicalTrials.gov registration of the ECHELON-1 trial (ABVD arm) [37]; the adaptive approach from RATHL [13] and the limited-stage schedule from the EHA guideline [25]. In RATHL, omitting bleomycin after a negative PET reduced pulmonary toxicity without a significant loss of efficacy, and radiotherapy was not recommended for patients with a negative interim PET [13].
Evidence: RATHL (2016)
PET-guided BrECADD (HD21 trial)
Newly diagnosed advanced-stage classic Hodgkin lymphoma (stage IIB with a large mediastinal mass and/or extranodal lesions, or stage III–IV); age 18 to 60 years without significant comorbidity (the recommended regimen for this group in the EHA guideline)Cycle length: Every 21 days
Newly diagnosed advanced-stage classic Hodgkin lymphoma (stage IIB with a large mediastinal mass and/or extranodal lesions, or stage III–IV); age 18 to 60 years without significant comorbidity (the recommended regimen for this group in the EHA guideline [25])
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Brentuximab vedotin | 1.8 mg/kg (for body weight above 100 kg, calculate using 100 kg) | IV (over 30 minutes) | Day 1 |
| Etoposide | 150 mg/m² | IV | Days 1–3 |
| Cyclophosphamide | 1250 mg/m² | IV | Day 1 |
| Doxorubicin | 40 mg/m² | IV | Day 1 |
| Dacarbazine | 250 mg/m² | IV | Days 2 and 3 |
| Dexamethasone | 40 mg | Oral | Days 1–4 |
Starting dose and dose-reduction levels from the EMA Summary of Product Characteristics [35]; administration days per the ClinicalTrials.gov registration NCT07002216 [36]; the PET and radiotherapy schedule from the EHA guideline [25]. Primary prophylactic G-CSF from day 5 of each cycle is mandatory; antibiotic prophylaxis three times a week throughout chemotherapy; in patients over 40 years, a 4-day dexamethasone prephase before the first cycle is recommended [35]. If toxicity events occur (leukopenia lasting more than 4 days, thrombocytopenia, grade 4 infection or toxicity, a delay of more than 2 weeks), the doses of the chemotherapy components are reduced by one level (e.g., cyclophosphamide 1250, 1100, 950, 800 and, at the lowest level, 650 mg/m²); in severe cytopenia, brentuximab is reduced to 1.2 mg/kg (maximum 120 mg) [35]. The 100 kg weight cap for calculating the brentuximab dose comes from the FDA label [34].
Escalated BEACOPP (eBEACOPP)
Unfavorable limited-stage Hodgkin lymphoma in patients aged 60 years or younger (2 cycles of eBEACOPP followed by 2 cycles of ABVD); treatment escalation after a positive interim PET on ABVDCycle length: Every 21 days
Unfavorable limited-stage Hodgkin lymphoma in patients aged 60 years or younger (2 cycles of eBEACOPP followed by 2 cycles of ABVD); treatment escalation after a positive interim PET on ABVD
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Etoposide | 200 mg/m² | IV | Days 1–3 |
| Doxorubicin | 35 mg/m² | IV | Day 1 |
| Cyclophosphamide | 1250 mg/m² | IV | Day 1 |
| Bleomycin | 10 mg/m² | IV | Day 8 |
| Vincristine | 1.4 mg/m² | IV | Day 8 |
| Procarbazine | 100 mg/m² | Oral | Days 1–7 |
| Prednisone | 40 mg/m² | Oral | Days 1–14 |
Doses from the abstract of the HD21 trial (eBEACOPP arm) [18]; its role in limited-stage disease from the EHA guideline [25]. The accelerated version (BEACOPP-14) is given with granulocyte growth factor support [13]. eBEACOPP carries a risk of permanent infertility, prolonged fatigue and myelodysplasia or acute leukemia [13].
Evidence: GHSG HD21 (2024), RATHL (2016)
BV-AVD (brentuximab vedotin + AVD; ECHELON-1 trial)
Adults with newly diagnosed stage III or IV classic Hodgkin lymphomaCycle length: Every 28 days
Adults with newly diagnosed stage III or IV classic Hodgkin lymphoma
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Brentuximab vedotin | 1.2 mg/kg (maximum 120 mg) | IV (over 30 minutes) | Days 1 and 15 |
| Doxorubicin | 25 mg/m² | IV | Days 1 and 15 |
| Vinblastine | 6 mg/m² | IV | Days 1 and 15 |
| Dacarbazine | 375 mg/m² | IV | Days 1 and 15 |
Pembrolizumab (KEYNOTE-204 trial)
Relapsed or refractory classic Hodgkin lymphoma in adults (ECOG 0–1) who have relapsed after autologous stem cell transplantation or are not transplant candidates
Relapsed or refractory classic Hodgkin lymphoma in adults (ECOG 0–1) who have relapsed after autologous stem cell transplantation or are not transplant candidates
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg every 3 weeks or 400 mg every 6 weeks (children: 2 mg/kg, maximum 200 mg, every 3 weeks) | IV | Day 1 |
In KEYNOTE-204, pembrolizumab 200 mg every 3 weeks was compared with brentuximab vedotin 1.8 mg/kg every 3 weeks [33]; treatment duration and the alternative dose from the FDA label [38]. Check liver enzymes, creatinine and thyroid function at baseline and periodically; for grade 4 hematologic toxicity in Hodgkin lymphoma, withhold the drug until recovery to grade 0–1 [38]. For transplant-eligible patients, the EHA guideline recommends checkpoint inhibitor–containing salvage therapy followed by high-dose chemotherapy and autologous stem cell transplantation [25].
Evidence: KEYNOTE-204 (2021)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Diffuse large B-cell lymphoma (DLBCL)
DLBCL is an aggressive lymphoma, but many patients achieve complete remission and are cured with first-line treatment. Adding the antibody rituximab to CHOP chemotherapy in older patients increased the complete response rate and reduced the risk of death [6]. The R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone; usually 6 cycles every 21 days) is the standard first-line treatment [6, 24, 39].
In patients at intermediate or high risk, replacing vincristine with polatuzumab vedotin (the Pola-R-CHP regimen) controlled the disease slightly better, but the difference in overall survival was not statistically significant [7]; the EHA guideline (2025) prefers Pola-R-CHP in these patients and considers R-CHOP an acceptable alternative [24].
Treatment of relapsed or refractory DLBCL
Salvage chemotherapy and autologous transplantation
Salvage chemoimmunotherapy (such as R-ICE, R-DHAP or R-GDP) followed, in patients who respond, by high-dose chemotherapy and autologous stem cell transplantation is the standard treatment for late relapse (more than 12 months after first-line treatment) [24]. In the CORAL and LY.12 trials, the salvage regimens had similar efficacy, and GDP caused fewer side effects and less need for hospitalization [23, 31]; the results of this approach are much poorer in early relapse [23].
Patients not eligible for transplantation
In patients who are not candidates for high-dose chemotherapy, R-GemOx (rituximab, gemcitabine and oxaliplatin) is one of the options recommended by the EHA guideline [24]. In the STARGLO trial, adding the bispecific antibody glofitamab to GemOx increased overall survival compared with R-GemOx [20].
CAR T-cell therapy in early relapse
In patients who relapse within 12 months of first-line treatment or whose disease is refractory, CAR T-cell therapy with axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel) gave better results than standard treatment (salvage chemotherapy and autologous transplantation) in the ZUMA-7 and TRANSFORM trials, and axi-cel also improved overall survival [8, 9, 19]. The EHA guideline considers these two products the recommended second-line treatment for early relapse [24].
Rituximab-containing regimens (R-CHOP, Pola-R-CHP, R-ICE, R-DHAP and R-GDP): before starting, hepatitis B screening (HBsAg and anti-HBc) and a complete blood count; premedication (acetaminophen and an antihistamine) before each infusion [41].
Anthracycline-containing regimens (R-CHOP and Pola-R-CHP): in patients with more than three cardiovascular risk factors, the EHA guideline recommends echocardiography at the end of anthracycline treatment and three months later [24].
For physicians
Treatment regimens and dosing: first-line DLBCL
R-CHOP-21
First-line DLBCL (standard treatment; for IPI 2 to 5, an acceptable alternative to Pola-R-CHP)Cycle length: Every 21 days
First-line DLBCL (standard treatment; for IPI 2 to 5, an acceptable alternative to Pola-R-CHP)
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Rituximab | 375 mg/m² | IV | Day 1 |
| Cyclophosphamide | 750 mg/m² | IV | Day 1 |
| Doxorubicin | 50 mg/m² | IV | Day 1 |
| Vincristine | 1.4 mg/m² (maximum 2 mg) | IV | Day 1 |
| Prednisone | 100 mg daily | Oral | Days 1–5 |
Doses from the full text of POLARIX (R-CHOP arm) [39]; the rituximab label for DLBCL specifies up to 8 infusions, on Day 1 of each cycle [41]. In POLARIX, primary prophylactic G-CSF was mandatory during the first 6 cycles, and central nervous system prophylaxis was permitted according to institutional practice [39].
Evidence: POLARIX (2022)
Pola-R-CHP (POLARIX trial)
First-line DLBCL with IPI 2 to 5, age 18 to 80 years, ECOG 0–2 (the EHA guideline’s preferred regimen for IPI 2 to 5)Cycle length: Every 21 days
First-line DLBCL with IPI 2 to 5, age 18 to 80 years, ECOG 0–2 (the EHA guideline’s preferred regimen for IPI 2 to 5)
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Polatuzumab vedotin | 1.8 mg/kg | IV | Day 1 |
| Rituximab | 375 mg/m² | IV | Day 1 |
| Cyclophosphamide | 750 mg/m² | IV | Day 1 |
| Doxorubicin | 50 mg/m² | IV | Day 1 |
| Prednisone | 100 mg daily | Oral | Days 1–5 |
Doses and eligibility criteria from the full text of POLARIX [39]; EHA preference [24]. Per the label: prophylactic G-CSF is mandatory; Pneumocystis and herpes prophylaxis throughout treatment; premedication with an antihistamine and an antipyretic; tumor lysis syndrome prophylaxis in high-risk patients. For neuropathy, the polatuzumab dose is reduced to 1.4 and then 1 mg/kg, and if it is discontinued, R-CHP is continued [40]. No clear benefit was seen in the subgroups aged under 60 years, with GCB type, with bulky disease or with lower IPI [39].
Evidence: POLARIX (2022)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment regimens and dosing: relapsed or refractory DLBCL, eligible for transplantation or CAR T-cell therapy
R-ICE or R-DHAP followed by BEAM and autologous transplantation (CORAL trial)
Relapsed or refractory DLBCL in transplant-eligible patients (especially late relapse, more than 12 months after first-line treatment)Cycle length: Every 21 days
Relapsed or refractory DLBCL in transplant-eligible patients (especially late relapse, more than 12 months after first-line treatment)
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| R-ICE | |||
| Rituximab | 375 mg/m² | IV | Day 1 (in the first cycle, an additional dose on Day −1) |
| Etoposide | 100 mg/m² daily | IV | Days 1–3 |
| Ifosfamide (with mesna) | 5000 mg/m² | IV (24-hour continuous infusion) | Day 2 |
| Carboplatin | AUC 5 (maximum 800 mg) | IV | Day 2 |
| R-DHAP | |||
| Rituximab | 375 mg/m² | IV | Day 1 (in the first cycle, an additional dose on Day −1) |
| Cisplatin | 100 mg/m² | IV (24-hour continuous infusion) | Day 1 |
| Cytarabine | 2 g/m² over 3 hours, twice, 12 hours apart | IV | Day 2 |
| Dexamethasone | 40 mg daily | Oral or IV | Days 1–4 |
| BEAM (transplant conditioning) | |||
| Carmustine | 300 mg/m² | IV | Day −6 |
| Etoposide | 200 mg/m² | IV | Days −5 to −2 |
| Cytarabine | 200 mg/m² | IV | Days −5 to −2 |
| Melphalan | 140 mg/m² | IV | Day −1 |
Doses from the full text of CORAL [23]. G-CSF was given after R-ICE, and after R-DHAP according to institutional practice, but always after the third cycle until stem cell collection was complete [23]. Response was much lower in patients relapsing earlier than 12 months after diagnosis [23], and in this group CAR T-cell therapy is the recommended second-line treatment [24].
R-GDP (LY.12 trial)
Relapsed or refractory DLBCL in transplant-eligible patients; a less toxic alternative to R-DHAP before autologous transplantationCycle length: Every 21 days
Relapsed or refractory DLBCL in transplant-eligible patients; a less toxic alternative to R-DHAP before autologous transplantation
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Rituximab | 375 mg/m² | IV | Day 1 |
| Cisplatin | 75 mg/m² | IV | Day 1 |
| Gemcitabine | 1000 mg/m² | IV | Days 1 and 8 |
| Dexamethasone | 40 mg daily | Oral or IV | Days 1–4 |
Evidence: NCIC-CTG LY.12 (2014)
Second-line CAR T-cell therapy: axicabtagene ciloleucel (ZUMA-7) or lisocabtagene maraleucel (TRANSFORM)
Large B-cell lymphoma refractory to first-line treatment or relapsing within 12 months of it (candidates for intensive therapy)Cycle length: Single dose
Large B-cell lymphoma refractory to first-line treatment or relapsing within 12 months of it (candidates for intensive therapy)
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Axi-cel: lymphodepletion | |||
| Cyclophosphamide | 500 mg/m² | IV | Days −5, −4 and −3 before infusion |
| Fludarabine | 30 mg/m² | IV | Days −5, −4 and −3 before infusion |
| Axi-cel | |||
| Axicabtagene ciloleucel | 2 × 10⁶ CAR-positive viable T cells/kg (maximum 2 × 10⁸ cells) | IV | Once, Day 0 |
| Liso-cel: lymphodepletion | |||
| Fludarabine | 30 mg/m² daily | IV | 3 days |
| Cyclophosphamide | 300 mg/m² daily | IV | 3 days |
| Liso-cel | |||
| Lisocabtagene maraleucel | 90 to 110 × 10⁶ CAR-positive viable T cells | IV | Once, 2 to 7 days after completion of lymphodepletion |
Doses from the FDA labels for YESCARTA and BREYANZI [44, 45]. Before infusion, acetaminophen and an H1 antihistamine; tocilizumab and emergency equipment must be available; the patient should stay near the treatment center for at least 2 weeks after axi-cel infusion [44]. In ZUMA-7, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21% of patients [8]. In renal impairment, adjust the fludarabine and cyclophosphamide doses according to the labels of these drugs [45].
Evidence: TRANSFORM (2025), ZUMA-7 (2023), ZUMA-7 (2022)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Rituximab-containing regimen (R-GemOx): before starting, hepatitis B screening (HBsAg and anti-HBc) and a complete blood count; premedication (acetaminophen and an antihistamine) before each infusion [41].
CD20×CD3 bispecific antibodies (glofitamab and epcoritamab): cytokine release syndrome (CRS) is the most common adverse event, mostly grade 1–2 and occurring in the first cycles; step-up dosing is used, and for glofitamab, pretreatment with obinutuzumab [10, 11].
For physicians
Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines
R-GemOx
Relapsed or refractory DLBCL in patients not eligible for high-dose chemotherapy and transplantationCycle length: Every 15 days
Relapsed or refractory DLBCL in patients not eligible for high-dose chemotherapy and transplantation
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Rituximab | 375 mg/m² | IV | Day 1 |
| Gemcitabine | 1000 mg/m² | IV | Day 2 |
| Oxaliplatin | 100 mg/m² | IV | Day 2 |
Doses from the full text of the LYSA group’s phase 2 trial [32]; its place in the EHA guideline [24]. No dose reductions were planned for hematologic toxicity; the next cycle was postponed until neutrophils reached 1.0 × 10⁹/L and platelets 100 × 10⁹/L; the oxaliplatin dose was adjusted for peripheral neuropathy [32].
Evidence: LYSA R-GemOx (2013)
Glofitamab + GemOx (STARGLO trial)
Relapsed or refractory DLBCL after one or more lines of therapy in patients who are not transplant candidatesCycle length: Every 21 days
Relapsed or refractory DLBCL after one or more lines of therapy in patients who are not transplant candidates
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pretreatment | |||
| Obinutuzumab | Single dose | IV | 7 days before the first glofitamab dose |
| Cycles 1–8 | |||
| Glofitamab | Step-up dosing to 30 mg | IV | Per protocol |
| Gemcitabine | 1000 mg/m² | IV | Each cycle (day per protocol) |
| Oxaliplatin | 100 mg/m² | IV | Each cycle (day per protocol) |
| Cycles 9–12 | |||
| Glofitamab | 30 mg | IV | Day 1 |
Doses from the abstract of the STARGLO trial [43] and obinutuzumab pretreatment from the trial registration; the exact days of step-up dosing and GemOx are given in the full text of the article. The obinutuzumab pretreatment dose in the glofitamab label is 1000 mg [46]. Premedication, tumor lysis syndrome prophylaxis and cytokine release syndrome monitoring are the same as for single-agent glofitamab [46].
Evidence: STARGLO (2024)
Single-agent glofitamab (fixed duration)
DLBCL or LBCL arising from follicular lymphoma, relapsed or refractory after at least 2 lines of systemic therapyCycle length: Every 21 days
DLBCL or LBCL arising from follicular lymphoma, relapsed or refractory after at least 2 lines of systemic therapy
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab (pretreatment) | 1000 mg | IV | Day 1 |
| Glofitamab (step-up dose 1) | 2.5 mg | IV | Day 8 |
| Glofitamab (step-up dose 2) | 10 mg | IV | Day 15 |
| Cycles 2–12 | |||
| Glofitamab | 30 mg | IV | Day 1 |
Per the FDA label for COLUMVI [46]: hospitalization during and for 24 hours after the 2.5 mg dose (and after the 10 mg dose if CRS of any grade occurred with the previous dose); premedication with dexamethasone 20 mg IV (cycle 1, Days 8 and 15; cycles 2 and 3), acetaminophen and an antihistamine; adequate hydration and tumor lysis syndrome prophylaxis in high-risk patients; antiviral prophylaxis against herpes and consideration of CMV and Pneumocystis prophylaxis. Dose reduction of glofitamab is not recommended. CRS occurred in 63% of patients in the trial [10].
Evidence: NP30179 (2022)
Single-agent epcoritamab
DLBCL or high-grade B-cell lymphoma, relapsed or refractory after at least 2 lines of systemic therapyCycle length: Every 28 days
DLBCL or high-grade B-cell lymphoma, relapsed or refractory after at least 2 lines of systemic therapy
Before prescribing: Shared safety points Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Epcoritamab | 0.16 mg (Day 1), 0.8 mg (Day 8), 48 mg (Days 15 and 22) | SC | Days 1, 8, 15 and 22 |
| Cycles 2 and 3 | |||
| Epcoritamab | 48 mg | SC | Days 1, 8, 15 and 22 |
| Cycles 4–9 | |||
| Epcoritamab | 48 mg | SC | Days 1 and 15 |
| Cycle 10 onward | |||
| Epcoritamab | 48 mg | SC | Day 1 |
Per the FDA label for EPKINLY [47]: in cycle 1, dexamethasone 15 mg (or prednisolone 100 mg) 30 to 120 minutes before each dose and for three days afterward, plus diphenhydramine and acetaminophen; Pneumocystis prophylaxis is mandatory and herpes prophylaxis is recommended; after the first 48 mg dose (cycle 1, Day 15), assess the need for hospitalization or outpatient monitoring. CRS occurred in 51% of patients, mostly grade 1–2 [11].
Evidence: EPCORE NHL-1 (2026)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Follicular lymphoma
Treatment of follicular lymphoma
Active surveillance
Follicular lymphoma is a slow-growing disease. In patients without symptoms and with a low disease burden, regular monitoring without immediate treatment is a standard and safe approach; in a British trial, nearly half of the patients in the surveillance group had not needed treatment by three years, and single-agent rituximab only delayed the time until new treatment was needed [14].
First-line treatment
Rituximab maintenance
In patients with a high tumor burden who responded to first-line treatment, continuing rituximab for two years significantly prolonged the time to disease progression, with no difference in overall survival [27].
Rituximab-containing regimens (BR, rituximab maintenance or monotherapy, and R2): before starting, hepatitis B screening (HBsAg and anti-HBc) and a complete blood count; premedication (acetaminophen and an antihistamine) before each infusion [41].
For physicians
Treatment regimens and dosing: follicular lymphoma
Bendamustine-rituximab (BR; StiL NHL1 trial)
Follicular lymphoma or other indolent lymphomas and mantle cell lymphoma requiring treatment, first lineCycle length: Every 28 days
Follicular lymphoma or other indolent lymphomas and mantle cell lymphoma requiring treatment, first line
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Bendamustine | 90 mg/m² | IV | Days 1 and 2 |
| Rituximab | 375 mg/m² | IV | Day 1 |
Doses from the StiL NHL1 trial [26]. Do not use bendamustine with creatinine clearance below 30 mL/min; the 120 mg/m² dose on the FDA label refers to monotherapy for rituximab-refractory indolent lymphoma, not to the BR regimen [48].
Evidence: StiL NHL1 (2013)
Rituximab maintenance (PRIMA trial) and single-agent rituximab
Maintenance: follicular lymphoma with a high tumor burden that has achieved a complete or partial response to induction immunochemotherapy; single agent: asymptomatic follicular lymphoma with a low tumor burden
Maintenance: follicular lymphoma with a high tumor burden that has achieved a complete or partial response to induction immunochemotherapy; single agent: asymptomatic follicular lymphoma with a low tumor burden
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Maintenance | |||
| Rituximab | 375 mg/m² | IV | Every 8 weeks, starting 8 weeks after the last induction cycle |
| Single agent | |||
| Rituximab | 375 mg/m² | IV | Weekly for 4 weeks |
Maintenance from PRIMA [27] and the FDA label [41]. Single-agent rituximab in asymptomatic low-volume lymphoma from the British trial; this treatment only delayed the time until new treatment was needed [14]. Active surveillance is also a standard approach for these patients [14].
Evidence: PRIMA (2019), Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial (2014)
Obinutuzumab + chemotherapy and maintenance (GALLIUM trial)
Previously untreated follicular lymphoma requiring treatment (replacing rituximab in immunochemotherapy)
Previously untreated follicular lymphoma requiring treatment (replacing rituximab in immunochemotherapy)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction | |||
| Obinutuzumab | 1000 mg | IV | Cycle 1: Days 1, 8 and 15; subsequent cycles: Day 1 |
| Partner chemotherapy | Bendamustine (6 cycles of 28 days) or CHOP (6 cycles of 21 days, followed by 2 cycles of obinutuzumab alone) or CVP (8 cycles of 21 days) | IV | Per regimen |
| Maintenance | |||
| Obinutuzumab | 1000 mg | IV | Every 2 months |
Per the FDA label for GAZYVA [49]: premedication before each infusion and tumor lysis syndrome prophylaxis; the cycle 1 infusion is started at 50 mg/hour and increased by 50 mg/hour every 30 minutes (up to 400 mg/hour); from cycle 2 onward, in the absence of a grade 3 or higher infusion-related reaction, a 90-minute infusion is possible.
Lenalidomide + rituximab (R2; AUGMENT trial)
Relapsed/refractory follicular lymphoma (grade 1 to 3a) or marginal zone lymphoma after at least one prior therapy, not refractory to rituximabCycle length: Every 28 days
Relapsed/refractory follicular lymphoma (grade 1 to 3a) or marginal zone lymphoma after at least one prior therapy, not refractory to rituximab
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lenalidomide | 20 mg daily (creatinine clearance 30 to 59 mL/min: 10 mg) | Oral | Days 1–21 |
| Rituximab | 375 mg/m² | IV | Cycle 1: Days 1, 8, 15 and 22; cycles 2–5: Day 1 |
Doses from the full text of AUGMENT [28]. Anticoagulant or antiplatelet prophylaxis was recommended for patients at risk of thromboembolism; growth factor use was permitted according to guidelines [28]. Per the label, after recovery from cytopenia the dose is reduced by 5 mg (not below 5 mg); with creatinine clearance of 30 to 60 mL/min, an increase to 15 mg is possible after 2 cycles if tolerated [50].
Evidence: AUGMENT (2019)
Single-agent mosunetuzumab (fixed duration)
Relapsed or refractory follicular lymphoma after at least 2 lines of systemic therapyCycle length: Every 21 days
Relapsed or refractory follicular lymphoma after at least 2 lines of systemic therapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Mosunetuzumab | 1 mg (Day 1), 2 mg (Day 8), 60 mg (Day 15) | IV (cycle 1 doses over at least 4 hours) | Days 1, 8 and 15 |
| Cycle 2 | |||
| Mosunetuzumab | 60 mg | IV | Day 1 |
| Cycle 3 onward | |||
| Mosunetuzumab | 30 mg | IV | Day 1 |
Per the FDA label for LUNSUMIO (intravenous formulation) [51]: premedication in cycles 1 and 2 with dexamethasone 20 mg IV (or methylprednisolone 80 mg), an antihistamine and acetaminophen; from cycle 3 onward, only after CRS with the previous dose; the patient should be well hydrated. The subcutaneous formulation (LUNSUMIO VELO) has different dosing and is not a direct substitute [51].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Mantle cell lymphoma
Mantle cell lymphoma is usually aggressive. In younger patients, the TRIANGLE trial showed that adding the oral drug ibrutinib to immunochemotherapy improves treatment outcomes and overall survival, and that omitting autologous transplantation in the ibrutinib group did not worsen outcomes [16]. In patients aged 65 years and older, adding ibrutinib to bendamustine-rituximab controlled the disease for longer, with no difference in overall survival [29].
At relapse, ibrutinib controlled the disease better than temsirolimus [30], and after failure of BTK inhibitors, CAR T-cell therapy with brexucabtagene autoleucel produced responses in most patients [21].
Ibrutinib (TRIANGLE, SHINE and RAY): risk of atrial fibrillation and bleeding; withhold for 3 to 7 days before and after surgery depending on bleeding risk; dose adjustment with CYP3A inhibitors and in hepatic impairment, and avoidance in severe hepatic impairment (current FDA label for other indications; this label does not include a mantle cell lymphoma indication) [52].
Rituximab-containing regimens (TRIANGLE and SHINE): before starting, hepatitis B screening (HBsAg and anti-HBc) and a complete blood count; premedication (acetaminophen and an antihistamine) before each infusion [41].
For physicians
Treatment regimens and dosing: mantle cell lymphoma
Ibrutinib + immunochemotherapy (TRIANGLE trial)
Previously untreated stage II–IV mantle cell lymphoma, age 18 to 65 years, eligible for autologous transplantation
Previously untreated stage II–IV mantle cell lymphoma, age 18 to 65 years, eligible for autologous transplantation
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| R-CHOP (alternating with R-DHAP) | |||
| Rituximab | 375 mg/m² | IV | Day 0 or 1 |
| Cyclophosphamide / doxorubicin | 750 / 50 mg/m² | IV | Day 1 |
| Vincristine | 1.4 mg/m² (maximum 2 mg) | IV | Day 1 |
| Prednisone | 100 mg | Oral | Days 1–5 |
| Ibrutinib | 560 mg daily | Oral | Days 1–19 |
| R-DHAP or R-DHAOx | |||
| Rituximab | 375 mg/m² | IV | Day 0 or 1 |
| Dexamethasone | 40 mg | IV or oral | Days 1–4 |
| Cytarabine | 2 g/m² over 3 hours, twice, 12 hours apart | IV | Day 2 |
| Cisplatin (or oxaliplatin 130 mg/m² in R-DHAOx) | 100 mg/m² over 24 hours | IV | Day 1 |
| Maintenance | |||
| Ibrutinib | 560 mg daily | Oral | Continuously for 2 years |
Doses from the TRIANGLE abstract (4.5-year follow-up) [16]. Adding transplantation to the ibrutinib-containing regimen increased grade 3–5 hematologic toxicity and infections during maintenance [16].
Evidence: TRIANGLE (2026)
Ibrutinib + BR and rituximab maintenance (SHINE trial)
Previously untreated mantle cell lymphoma in patients aged 65 years and olderEach drug’s schedule in the table
Previously untreated mantle cell lymphoma in patients aged 65 years and older
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ibrutinib | 560 mg once daily | Oral | Continuous |
| Bendamustine | 90 mg/m² | IV | Days 1 and 2, every 28 days (6 cycles) |
| Rituximab | 375 mg/m² | IV | Every 28 days (6 cycles) |
| Maintenance (complete or partial response) | |||
| Rituximab | 375 mg/m² | IV | Every 8 weeks for up to 12 doses |
Doses from the SHINE abstract [29]; the BR schedule (Days 1 and 2 every 28 days) follows the standard regimen [26].
Evidence: SHINE (2022), StiL NHL1 (2013)
Single-agent ibrutinib in relapsed mantle cell lymphoma (RAY trial)
Relapsed or refractory mantle cell lymphoma after at least one rituximab-containing therapyCycle length: Continuous
Relapsed or refractory mantle cell lymphoma after at least one rituximab-containing therapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ibrutinib | 560 mg once daily | Oral | Continuous |
Dose from the RAY trial (versus temsirolimus) [30].
Evidence: RAY (MCL3001) (2016)
Brexucabtagene autoleucel (CAR T-cell therapy; ZUMA-2 trial)
Relapsed or refractory mantle cell lymphoma, including after failure of a BTK inhibitorCycle length: Single dose
Relapsed or refractory mantle cell lymphoma, including after failure of a BTK inhibitor
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lymphodepletion | |||
| Cyclophosphamide | 500 mg/m² | IV | Days −5, −4 and −3 before infusion |
| Fludarabine | 30 mg/m² | IV | Days −5, −4 and −3 before infusion |
| Brexucabtagene autoleucel | 2 × 10⁶ CAR-positive viable T cells/kg (maximum 2 × 10⁸ cells) | IV | Once, Day 0 |
Doses from the FDA label for TECARTUS [53]; results from ZUMA-2 [21]. Monitoring for cytokine release syndrome and neurologic toxicities as with other CAR T-cell products [53].
Evidence: ZUMA-2 (2023)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Marginal zone lymphoma
Marginal zone lymphoma is slow-growing and has extranodal (MALT), splenic and nodal types [17]. In gastric MALT lymphoma associated with Helicobacter pylori, eradicating the bacterium with antibiotics is the first-line treatment, and many patients go into remission with this treatment alone. In other cases, local radiotherapy, rituximab or immunochemotherapy is used, depending on the site and extent of the disease [17, 22]. The AUGMENT trial, which studied the combination of lenalidomide and rituximab (R2) at relapse, also included patients with marginal zone lymphoma [28]; details of this regimen are given in the follicular lymphoma section.
What should I do after diagnosis?
Frequently asked questions
Is lymphoma curable?
Many lymphomas can be cured. For example, in advanced Hodgkin lymphoma, six-year survival of more than 90% has been reported with modern regimens [4], and a large proportion of patients with DLBCL recover with first-line treatment [7]. Slow-growing lymphomas such as follicular lymphoma are usually a chronic disease that can be kept under control for years [15].
What is the difference between Hodgkin and non-Hodgkin lymphoma?
The main difference is the type of cancer cells seen under the microscope; Hodgkin lymphoma has characteristic Reed–Sternberg cells. The two groups differ in their treatment, course and outlook [1].
Why isn’t my doctor treating my follicular lymphoma?
In follicular lymphoma that causes no symptoms and is low in volume, active surveillance is a standard and safe approach, and treatment is started if symptoms appear or the disease progresses [14].
If lymphoma comes back, what treatments are available?
A relapse of lymphoma does not mean that treatment options have run out. In DLBCL, salvage chemotherapy and autologous stem cell transplantation is the standard treatment for eligible patients [23, 24]. In patients who relapse less than 12 months after their first treatment or whose disease does not respond to it, CAR T-cell therapy has given better results in trials and is the recommended second-line treatment in guidelines [8, 9, 24]. In follicular and mantle cell lymphomas, chemotherapy-free combinations such as lenalidomide-rituximab and the oral drug ibrutinib are also used [28, 30].
Recent evidence and advances (for physicians)
For physicians
Hodgkin lymphoma: first line and relapse
- N-AVD: In S1826 (994 patients, age 12 years and older, stages III–IV), N-AVD was superior to BV-AVD: two-year progression-free survival 92% vs 83% (HR 0.45) [5].
- BrECADD: In HD21, PET-guided BrECADD compared with eBEACOPP was associated with higher four-year progression-free survival (94.3% vs 90.9%) and less treatment-related morbidity (42% vs 59%) [18].
- BV-AVD: In ECHELON-1 (median follow-up 73 months), six-year overall survival was 93.9% with BV-AVD vs 89.4% with ABVD (HR for death 0.59) [4].
- PET-guided ABVD: In RATHL, 83.7% of patients had a negative PET after two cycles of ABVD [13].
- Relapse: In KEYNOTE-204, pembrolizumab compared with brentuximab vedotin increased median progression-free survival from 8.3 to 13.2 months [33].
DLBCL: first line
- In GELA LNH98-5 (older patients), adding rituximab to CHOP increased the complete response rate from 63% to 76% and reduced the risk of death [6].
- In the five-year follow-up of POLARIX (IPI 2 to 5), Pola-R-CHP increased five-year progression-free survival from 59.1% to 64.9% (HR 0.77), but the difference in overall survival was not statistically significant (HR 0.85) [7].
DLBCL: relapse, CAR T-cell therapy and bispecific antibodies
- Salvage therapy: In CORAL, responses to R-ICE and R-DHAP were similar (63.5% and 62.8%), but in relapse or refractory disease earlier than 12 months after diagnosis, the response rate was 46% vs 88% [23]. In LY.12, GDP was noninferior to DHAP in response and transplantation rate, had similar survival, and was associated with less toxicity, less need for hospitalization and better quality of life [31].
- Transplant-ineligible patients: In the LYSA group’s phase 2 trial, after four cycles of R-GemOx, 44% of patients had a complete response and 61% an overall response, although responses were lower in early relapse and after prior rituximab treatment [32]. In STARGLO (three-year follow-up), glofitamab + GemOx increased median overall survival to 25.5 months vs 12.5 months with R-GemOx [20].
- Second-line CAR T-cell therapy: In ZUMA-7, axi-cel increased 24-month event-free survival to 41% vs 16% with chemotherapy and autologous transplantation [8], and it was the first randomized trial to show an overall survival advantage of CAR T-cell therapy over standard treatment: four-year overall survival 54.6% vs 46.0% (HR for death 0.73) [19]. In TRANSFORM, with three-year follow-up, median event-free survival was 29.5 months vs 2.4 months, 36-month progression-free survival was 51% vs 26.5%, and the hazard ratio for overall survival after adjustment for crossover to the CAR T-cell arm was 0.566 [9].
- Bispecific antibodies in later lines: Fixed-duration glofitamab produced complete responses in 39% of patients with at least two prior lines of therapy, including patients previously treated with CAR T cells [10]; epcoritamab, with a median follow-up of about three years, achieved an overall response rate of 59% and a complete response rate of 41% [11].
Follicular lymphoma: first line, maintenance and relapse
- In StiL NHL1 (indolent and mantle cell lymphomas), bendamustine-rituximab compared with R-CHOP increased median progression-free survival from 31.2 to 69.5 months and had fewer side effects [26].
- In PRIMA, two years of rituximab maintenance increased median progression-free survival from 4.1 to 10.5 years, with no difference in overall survival [27]; in GALLIUM, obinutuzumab increased seven-year progression-free survival to 63.4% vs 55.7% with rituximab, but overall survival was similar [15].
- Relapse: In AUGMENT, lenalidomide + rituximab increased median progression-free survival from 14.1 to 39.4 months [28].
Mantle cell lymphoma: first line and relapse
- In TRIANGLE (younger patients, 4.5-year follow-up), adding ibrutinib to immunochemotherapy increased four-year failure-free survival from 70% to 82%; omitting autologous transplantation in the ibrutinib group did not worsen outcomes (81%), and four-year overall survival was higher in both ibrutinib groups (88% and 90% vs 81%) [16].
- In SHINE (65 years and older), adding ibrutinib to bendamustine-rituximab and rituximab maintenance increased median progression-free survival from 52.9 to 80.6 months, with no difference in overall survival [29].
- Relapse: In RAY, ibrutinib compared with temsirolimus increased median progression-free survival from 6.2 to 14.6 months [30].
European guidelines
The ESMO Clinical Practice Guideline for lymphomas (2025) brings together recommendations and management algorithms for DLBCL, follicular lymphoma, Hodgkin lymphoma, mantle cell lymphoma, marginal zone lymphoma, primary central nervous system lymphoma and peripheral T-cell lymphomas in a single document [22]; the EHA guidelines for large B-cell lymphoma (2025) and Hodgkin lymphoma (2026) are the latest disease-specific recommendations for these two diseases [24, 25].
Scientific evidence
Key studies
21 itemsNivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma
Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma
CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma
Addition of autologous stem-cell transplantation to an ibrutinib-containing first-line treatment in patients aged 18-65 years with mantle cell lymphoma (TRIANGLE): 4·5-year follow-up of a three-arm, randomised, open-label, phase 3 superiority trial of the European MCL Network
Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.
Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial.
Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study.
AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma
Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12
Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial.
Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.
Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial
Five-Year Outcomes of the POLARIX Study Comparing Pola-R-CHP and R-CHOP in Patients With Diffuse Large B-Cell Lymphoma
Glofitamab plus gemcitabine and oxaliplatin for relapsed/refractory DLBCL: 3-year follow-up of STARGLO.
Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study
Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma
Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study
Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma
Lisocabtagene Maraleucel Versus Standard of Care for Second-Line Relapsed/Refractory Large B-Cell Lymphoma: 3-Year Follow-Up From the Randomized, Phase III TRANSFORM Study
Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Efficacy and safety of epcoritamab in relapsed or refractory large B-cell lymphoma: 3-year update from the EPCORE NHL-1 trial.
Clinical guidelines
4 itemsHodgkin lymphoma: EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up.
Large B-cell lymphoma (LBCL): EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up.
Lymphomas: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification
References
53 referencesShow all references, 34 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 16Addition of autologous stem-cell transplantation to an ibrutinib-containing first-line treatment in patients aged 18-65 years with mantle cell lymphoma (TRIANGLE): 4·5-year follow-up of a three-arm, randomised, open-label, phase 3 superiority trial of the European MCL Network
- 17
- 18
- 19
- 20Glofitamab plus gemcitabine and oxaliplatin for relapsed/refractory DLBCL: 3-year follow-up of STARGLO
- 21
- 22
- 23
- 24
- 25
- 26
- 27
- 28
- 29
- 30
- 31
- 32
- 33
- 34
- 35
- 36A Phase 2 Trial of Abbreviated BrECADD Therapy in Stage 2B-IV Hodgkin Lymphoma (NCT07002216) — arms and interventions
- 37
- 38
- 39
- 40POLIVY (polatuzumab vedotin) for injection — Prescribing Information
- 41
- 42Phase IB Study of Oral Selinexor in Combination with Rituximab and Platinum Chemotherapy in Patients with Relapsed/Refractory B-Cell Lymphoma—Final Analysis
- 43Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial
- 44
- 45
- 46
- 47EPKINLY (epcoritamab-bysp) injection — Prescribing Information
- 48TREANDA (bendamustine hydrochloride) injection — Prescribing Information
- 49GAZYVA (obinutuzumab) injection — Prescribing Information
- 50REVLIMID (lenalidomide) capsules — Prescribing Information
- 51
- 52IMBRUVICA (ibrutinib) — Prescribing Information
- 53
This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.