Blood cancers

Role for cytarabine in MCL but questions remain: expert

Results from a landmark clinical trial are likely to cement in place the role of cytarabine in front-line therapy for younger patients with mantle cell lymphoma, but a lingering question remains, an expert says.

The phase 3 study from the European Mantle Cell Lymphoma Network founded in 1996 involved 497 patients aged under 65 years with newly diagnosed mantle cell lymphoma.

Patients were randomised to receive standard rituximab plus CHOP (R-CHOP) for six cycles (control group) or six cycles of alternating R-CHOP and rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP; cytarabine group), with both groups undergoing consolidative autologous stem-cell transplantation.

Both groups had similar overall response rates but patients in the cytarabine group had deeper remissions, the researchers reported their paper published in The Lancet.

This included a higher proportion of patients with negativity for minimal residual disease in peripheral blood and the bone marrow.

The risk of treatment failure was also reduced (hazard ratio 0·56, p=0·038), prolonging the median time to treatment failure from 3·9 years (95% CI 3·2–4·4) to 9·1 years (6·3–not reached).

The addition of cytarabine increased haematological toxicity and febrile neutropenia, and the addition of cisplatin significantly increased the rate of renal toxicity (p<0·0001).

However, overall survival was similar between both groups: (69% [95% CI 62–74] in the control group vs 76%[70–81] in the cytarabine group;p=0·12).

Treatment-related mortality was also similar in both groups (eight [3·4%] in both groups).

According to the authors the trial provided evidence that immunochemotherapy containing high-dose cytarabine followed by autologous stem-cell transplantation should be considered standard of care  in patients with mantle cell lymphoma up to the age of 65 years.

Writing in an accompanying editorial lymphoma expert Peter Martin from the Weill Cornell Medical College in New York said the trial was a success by “almost all measures” but the absence of a survival benefit was a “lingering question”.

“Treatments that improve response depth or duration but not survival might have value that is not immediately apparent, but results must be assessed in the context of toxicity and effect on subsequent therapies,” he said.

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