Thursday, November 6, 2014

Early Relapse After SCT Important for Prognosis in Multiple Myeloma

Patients who experienced early relapse of their multiple myeloma after undergoing autologous stem cell transplantation had worse overall survival and progression-free survival compared with those patients with a longer time to relapse, according to the results of a study published in Bone Marrow Transplantation.

“We conclude that early relapse after autologous stem cell transplantation appears to be a major prognostic variable in multiple myeloma,” wrote researchers led by Victor H. Jimenez-Zepeda, MD, of Princess Margaret Cancer Centre, Toronto. “Patients with early relapse post-autologous stem cell transplantation should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.”

According to the study, prior research has identified several factors associated with worse outcomes in the post-transplant realm, including elevated plasma cell labeling index, more than one treatment regimen prior to transplant, failure to achieve a complete response, and loss of complete response within 1 year of transplant.

In this study, Jimenez-Zepeda and colleagues analyzed the effects of early relapse on survival. They evaluated 184 consecutive patients with multiple myeloma who underwent single autologous stem cell transplantation between January 2002 and September 2012 and had novel induction therapy.

Of these patients, 15.3% achieved a complete response and 57.1% achieved a very good partial response at day 100 post-transplant. A smaller percentage of patients with early relapse had a very good partial response or better compared with those without early relapse (38% vs 70%; P = .008) at day 100 post-transplant.

The median progression-free survival for the group analyzed was 25.4 months. The median time to relapse was 17.2 months. Early relapse occurred in 36% of the patients who relapsed and was most common in patients treated with thalidomide induction regimens. According to the researchers, this result suggests that “second-generation immunomodulatory drugs and proteasome inhibitors might be better options to prevent early relapse to occur in the setting of autologous stem cell transplantation.”

Patients with early relapse had a median overall survival of 20 months compared with 93 months for those without early relapse (P = .001). Even among patients with a very good partial response who experienced early relapse, overall survival was significantly shorter than those patients who achieved the same level of response but without early relapse (38.53 months vs 79.3 months; P = .013).

The researchers evaluated the prognostic value of cytogenetic features on outcomes, but found that only a single case in the 27 early relapses had high-risk cytogenetics.

Finally, the researchers examined outcomes adjusted for age, best response to induction therapy, best response at day 100 post-transplant, and other variables, and found that early relapse was a major independent prognostic factor for overall survival in these patients.

“As patients with early relapse exhibited a lower rate of very good partial response or higher, new-generation drugs and strategies such as consolidation or maintenance should be considered especially for those patients where there is a high tumor burden,” the researchers wrote. “Studies on minimal residual disease and a more broad and deep panel of cytogenetics will help identifying some intrinsic biological factors that could be associated with lack of response sustainability.”

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