The initial response to therapy in a patient with newly diagnosed, symptomatic multiple myeloma (MM) can impact long-term treatment response and survival, but it is unclear which characteristics can predict an early and deep response to treatment in this patient population – both of which are associated with longer survival in MM patients.
To answer this question, a recent study published in the American Journal of Hematology by Moritz Binder, MD, MPH, and colleagues from the Mayo Clinic in Rochester, Minnesota, studied 1,304 patients with newly diagnosed MM who were treated between 2001 and 2013.
Multivariable logistic regression was used to assess the associations between baseline laboratory parameters and early, deep response (defined as a very good partial response or better [VGPR+]); multivariable proportional hazard regression was used to assess the association between initial response and overall survival (OS).
In the entire cohort, the following baseline characteristics were associated with an increased odds of achieving VGPR+ within four treatment cycles:
- Greater absolute free light chain (FLC) differences (odds ratio [OR] = 2.38; 95% CI 1.48-3.82)
- Patients younger in age (OR=2.18; 95% CI, 1.28-3.71)
- Lower hemoglobin levels (OR=1.68; 95% CI 1.12-2.54)
- IgA myeloma (OR=1.66; 95% CI 1.10-2.51)
“Both disease and patient factors were associated with better response early on,” Dr. Binder told ASH Clinical News, “and these factors were different for regimens containing immunomodulators and proteasome inhibitors.” In patients receiving proteasome inhibitors, the following parameters were associated with a better treatment response:
- Higher creatinine (OR=3.83; 95% CI 1.37-10.1)
- Lower calcium (OR=3.37; 95% CI 1.35-8.35)
- Greater absolute FLC differences (OR=2.50; 95% CI 1.10-5.71)
“Patients with better responses early in their course of treatment experienced longer overall survival,” Dr. Binder added. In a landmark analysis at four months from diagnosis, achieving VGPR+ was associated with decreased risk of subsequent mortality (hazard ratio = 0.69; 95% CI 0.53-0.86).
“This study was a first step in identifying factors that determine early response to treatment in patients with newly diagnosed disease,” Dr. Binder said. “These results will help to improve our understanding of the underlying complex disease biology that makes the treatment of multiple myeloma an ongoing challenge.”
Dr. Binder noted one limitation of the study: its retrospective design. “While these findings are intriguing, the suitability of these biomarkers needs to be evaluated in prospective studies before drawing firm conclusions and making definitive treatment recommendations,” he said. “Eventually, an individualized approach to treatment would be desirable, allowing us to maximize the therapeutic benefit of the currently available chemotherapy agents.”
Binder M, Rajkumar SV, Gertz MA, et al. Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma. Am J Hematol. 2015 July 6. [Epub ahead of print]