Clinical trialPhase 2Lymphoma

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.

Haematologica · 201349 patients (6 refractory, 43 relapsed)

Mounier N, El Gnaoui T, Tilly H, et al. Haematologica. 2013. 98:1726-1731

Study type: Clinical trial
Study name: LYSA R-GemOx
Phase: Phase 2
Design: Single-arm, multicentre phase 2 trial
Sample size: 49 patients (6 refractory, 43 relapsed)
Source: Haematologica · 2013
Trial registration: NCT00169195

In plain words

This study included 49 patients with diffuse large B-cell lymphoma whose disease had come back or had not responded to treatment, and who could not have high-dose chemotherapy and a transplant because of age or other conditions (median age 69). They received the combination of rituximab, gemcitabine and oxaliplatin (R-GemOx). About six in ten patients responded to treatment after four cycles, and about four in ten went into complete remission. The treatment was well tolerated, but in most patients the disease came back over time, and after 5 years about 14% were alive. Response was lower in those whose disease came back very early (less than a year) or who had already had rituximab.

Key results

61%

Overall response rate after 4 cycles

21 patients (44%) complete response and 8 patients (17%) partial response

18% in early relapse (less than 1 year) vs 54%

Overall response by time to progression/relapse

P=0.001

23% vs 65%

Overall response by prior rituximab exposure

With and without prior rituximab; P=0.004

12.8% / 13.9%

5-year progression-free survival / overall survival

Drugs in this study:Gemcitabine (Gemzar)Oxaliplatin (Eloxatin)Rituximab (Rituxan/MabThera)

Dose and schedule cards

R-GemOx

Relapsed or refractory DLBCL in patients not eligible for high-dose chemotherapy and transplantationCycle length: Every 15 daysOn the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines

Relapsed or refractory DLBCL in patients not eligible for high-dose chemotherapy and transplantation

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

Cycle length: Every 15 days
Duration: 8 cycles, if at least a partial response is achieved after 4 cycles

Doses from the full text of the LYSA group’s phase 2 trial; its place in the EHA guideline. No dose reductions were planned for haematologic 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.

On the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines

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 arms and regimens

1R-GemOx

Rituximab 375 mg/m² on day 1, gemcitabine 1000 mg/m² and oxaliplatin 100 mg/m² on day 2; repeated every 15 days. Four cycles, and a total of eight cycles in patients who had at least a partial response after four cycles. No dose reduction was planned for haematological toxicity, and the next cycle was delayed until neutrophils reached 1.0 × 10⁹/L and platelets 100 × 10⁹/L; the oxaliplatin dose was adjusted for peripheral neuropathy.

Source of the regimen details: Full text of the paper in PMC (PMC3815173), Methods section

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL) who were not candidates for high-dose therapy. Median age was 69 years; 31 (63%) had previously received rituximab and 17 (35%) an autologous transplant, and the International Prognostic Index (IPI) at entry was greater than 2 in 34 patients (71%).

Endpoints

Primary outcome: overall response rate after four cycles of treatment.

Other outcomes: progression-free survival, overall survival and tolerability.

Safety and side effects

The regimen was well tolerated; grade 3–4 infection occurred in 22% of cycles.

Clinical significance and place in guidelines

This multicentre trial showed that R-GemOx is a tolerable regimen with a consistent response rate in patients with refractory or relapsed DLBCL who are not candidates for high-dose therapy; it therefore became a reference regimen in this group and a backbone for combination with new drugs (and the comparator in later trials). However, long-term survival with this regimen alone is low.

Limitations

Single-arm study without a control group and with a small number of patients (49). Most patients were treated before the era of widespread first-line rituximab use (only 63% had prior rituximab), and response was significantly lower in patients with prior rituximab, which limits generalisation of the results to today's patients.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.