Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.
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Histopathological image of multiple myeloma. Smear preparation of bone marrow aspirate stained with May-Grünwald-Giemsa procedure.
Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.
The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.
Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.
Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.
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The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.
In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).
The researchers also analyzed the groups based on whether they received novel or older agents during induction.
Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).
Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.
“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.
The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.
The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”
Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.
SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.
