Induction Therapy

Most newly diagnosed patients have more aggressive MCL and must undergo induction therapy. Comorbidities and patient preference preclude intensive therapy for approximately 75% of newly diagnosed patients with MCL.

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Intensive induction regimens that include high-dose cytarabine are considered for more fit and younger patients in the hope of achieving durable remission, according to Dr Martin and his co-authors.

“High-dose cytarabine has a proven benefit as part of induction therapy in younger, fitter patients,” they noted. “Interestingly, high-dose cytarabine alone does not appear to be sufficient therapy for newly diagnosed MCL, which led to the early closure of the Nordic Lymphoma Group MCL-5 study.”

Compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) alone, R-CHOP administered in alternating cycles with a high-dose cytarabine regimen (rituximab, dexamethasone, high-dose cytarabine, and cisplatin [R-DHAP]) followed by autologous stem cell transplantation (ASCT) yielded higher complete-response rates (55% vs 39%; P = 0.0005) and no-minimal residual disease rates (79% vs 47%; P = 0.0001) in a phase 3 clinical trial — and a time-to-treatment-failure (TTF) of 9.1 years vs 4 years for R-CHOP alone.1,6

For patients who are not candidates for intensive induction therapy, there are several alternative immunochemotherapy regimens.

Bendamustine plus rituximab (BR) appears to also be non-inferior to R-CHOP, and possibly better tolerated.1,7 Replacing vincristine with bortezomib in R-CHOP (VR-CAP) was associated with a longer PFS but greater hematologic toxicity than R-CHOP (PFS: 24 vs 14 months; P < 0.001).1,8

“Several recent and ongoing trials are building on the BR backbone, so hopefully we will have more options in the near future,” Dr Martin said.

Consolidation Therapy

Younger and fitter patients may be eligible for high-dose consolidation chemotherapy and ASCT. Based on data from a single phase 3 trial, it is “reasonable to consider ASCT as a standard of care for younger, fitter patients,” Dr Martin’s team reported.

“It should be noted, however, that these data were generated prior to the widespread use of rituximab and incorporation of high-dose cytarabine into induction regimes,” Dr Martin told Cancer Therapy Advisor.

Maintenance Therapy

Post-consolidation maintenance therapy is administered with the goal of delaying MCL relapse among patients who have achieved remission. Rituximab is the “only standard of care maintenance drug” for MCL.1

The emerging roles for the angiogenesis inhibitor, lenalidomide, and the irreversible Bruton’s tyrosine kinase inhibitor, ibrutinib, in maintenance therapy are not yet clear, Dr Martin told Cancer Therapy Advisor.

“In all honesty, I’m not sure what to expect,” Dr Martin said. “Both drugs are active in MCL but neither has resulted in improved overall survival in phase 3 trials in the relapsed/refractory setting. Maybe they will get there in the maintenance setting but I admit I’m a little skeptical.

“I think it’s easy enough to predict that both drugs can improve PFS [progression-free survival] and both drugs are associated with side effects. Whether the PFS benefit is sufficient to warrant the side effects is the big question.”

Dr Martin is studying whether treatment-pause “drug holidays” reduce toxicity rates and improve patients’ quality of life — though it’s too soon for clinicians to consider this practice an option for patients with MCL.

“At Weill Cornell we are in the process of exploring this concept. I think it has to be done carefully.”