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Bendamustine regimen may be induction-therapy option in mantle cell lymphoma

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Is BR induction with a more intense regimen worth studying?

Young, fit patients with mantle cell lymphoma (MCL) are often treated with intensive, though non-curative, therapy. While some centers still use R-HyperCVAD/MA alone, most use alternating R-CHOP-based and high dose cytarabine-based regimens, followed by SCT. The U.S. Intergroup trial, led by SWOG, was designed to gather information about a strategy using a limited number of cycles of R-HyperCVAD/MA followed by SCT, and an alternative strategy using an effective but less-intense induction, bendamustine-rituximab (BR), also followed by SCT. The R-HyperCVAD/MA arm was closed early due to difficulties with stem cell collection. While there are technical reasons for this that likely could be overcome, results with other pre-SCT regimens are good enough that this is not likely to be further studied. The BR followed by SCT arm was closed after accrual of 35 patients, enough to get a sense that this was feasible, although it will be important to see further updates regarding how many of these patients did go on to SCT, and their ultimate outcomes. A key question is whether a study comparing BR induction with a different, commonly used intense regimen pre-SCT is worth the commitment of resources, given the range of novel agents now available for MCL.

Dr. Mitchell Smith is a medical oncologist affiliated with the Cleveland Clinic.


 

FROM 13-ICML

References

Rituximab plus bendamustine may prove to be an induction-therapy option for younger patients with mantle cell lymphoma, Dr. Richard Chen and his colleagues in a SWOG (Southwest Oncology Group) trial reported at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

Compared with a more aggressive combination regimen, a rituximab plus bendamustine (Treanda) option is a simple regimen that can be given in an outpatient setting and was associated with fewer adverse events and similar 2-year outcomes, the researchers found. The more aggressive regimen, however, was associated with lower-than-expected stem cell mobilization rates and the trial was prematurely closed, allowing no significant results.

Intermediate magnification micrograph of mantle cell lymphoma of the terminal ileum. Courtesy Wikimedia Commons/Nephron/Creative Commons

Intermediate magnification micrograph of mantle cell lymphoma of the terminal ileum.

For this study, two induction-therapy regimens were compared in 53 patients with untreated stage III or IV (or bulky stage II) mantle cell lymphoma. All patients were less than age 65 years and received rituximab (R) in combination with one of two regimens: 18 patients received four cycles of R-HyperCVAD + methotrexate + cytarabine (R-HyperCVAD/MTX/ARA-C) and 35 patients received six cycles of R-bendamustine.

The overall response rate was 94% with R-HyperCVAD/MTX/ARA-C and 86% with R-bendamustine; the complete response rates were 31% and 43%, respectively; the partial response rates were 62% and 43%, respectively, Dr. Chen and his associates reported.

The median follow-up for surviving patients is nearly 24 months. The estimated 2-year progression-free survival was 87% for patients in both treatment groups.

Significantly higher rates of bone marrow toxicity occurred in the group receiving the R-HyperCVAD/MTX/ARA-C regimen, compared with the bendamustine regimen. Grade 3 and 4 thrombocytopenia occurred in 69% given R-HyperCVAD/MTX/ARA-C and 17% given R-bendamustine. Anemia affected 56% of those given R-HyperCVAD/MTX/ARA-C and 8.6% given R-bendamustine. Neutropenia was seen in 63% given R-HyperCVAD/MTX/ARA-C and 34% of patients given R-bendamustine. Febrile neutropenia occurred in 31% given R-HyperCVAD/MTX/ARA-C and 14% given R-bendamustine.

The study was discontinued prematurely because of the low mobilization of stem cells at the transplant phase of the study in patients given R-HyperCVAD/MTX/ARA-C. Just 4 of 16 patients on R-HyperCVAD/MTX/ARA-C and 21 of 35 patients given R-bendamustine underwent autologous stem cell transplants.

The R-bendamustine regimen seems less myelosuppressive. Because of the premature closure of the trial, the study did not reach statistical significance for 2-year progression-free survival, the researchers reported. Since bendamustine in combination with rituximab was associated with lower rates of hematologic toxicity, however, it warrants further study as an induction regimen, they concluded.

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