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Induction triplets comparably effective, safe for newly diagnosed myeloma
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CHICAGO — Two lenalidomide-based induction triplets appeared similarly effective and safe for patients with newly diagnosed myeloma who underwent autologous stem cell transplant, according to randomized study results presented at the ASCO Annual Meeting.
Autologous stem cell transplant remains standard for younger, medically fit patients with newly diagnosed myeloma. Induction triplets with at least one newer compound prior to transplant is recommended, according to study background.
One of the most effective induction regimens is VRD, which consists of bortezomib (Velcade; Takeda, Millennium), lenalidomide (Revlimid, Celgene) and dexamethasone. However, induction with the RAD regimen — which consists of lenalidomide, dexamethasone and doxorubicin (Adriamycin, Rubex) — prior to stem cell transplant also has demonstrated encouraging efficacy with low toxicity.
Stefan Knop, MD, of Würzburg University Medical Center in Germany, and colleagues conducted the randomized, controlled DSMM XIV study to compare the two induction regimens.
The trial — which featured a 2 x 2 factorial design — included 476 patients aged up to 65 years with newly diagnosed myeloma randomly assigned to one of the two regimens between May 2012 and June 2016. Nearly one-fifth (18.3%) of patients had International Staging System stage III myeloma, 17.2% had elevated serum lactate dehydrogenase levels, 11.3% had deletion 17p, 11.1% had t(4;14) translocation and 4% had t(14;16) translocation.
Complete remission rate after induction served as the efficacy endpoint for the initial study phase. Knop and colleagues estimated a 20% complete remission rate with VRD, and they hypothesized that the complete remission rate with RAD would be noninferior. Researchers used eight-color flow cytometry on marrow samples to assess minimal residual disease.
The final analysis included 469 patients (median age, 55 years; range, 32-65) who received at least one dose of their assigned regimen. Of these, 232 received three 4-week RAD cycles and 237 received three 3-week VRD cycles.
A higher percentage of patients assigned VRD completed all induction cycles (93.2% vs. 89.7%).
Researchers reported a higher postinduction complete remission rate with VRD (13%; 90% CI, 8.9-18) than RAD (11.8%; 90% CI, 7.9-16.3), but the difference did not reach statistical significance.
“We were surprised to see how well patients with RAD induction fared where one had anticipated a clear-cut superiority in terms of response with VRD,” Knop told HemOnc Today. “It seems to be more than a direct comparison of bortezomib vs. anthracycline, and one aspect might be the higher cumulative dose of lenalidomide and a higher yet tolerable dexamethasone dose. We are eager to see time-dependent endpoints in correlation with molecular prognostic features.”
Results showed no significant difference in incidence of treatment-emergent serious adverse events between patients assigned the RAD and VRD regimens (20.3% vs. 14.8%). Researchers reported one case of treatment-related induction mortality — a cardiac arrest — in the VRD group, equating to an overall rate of 0.2%.
In the entire cohort, 72 of 317 patients (22.7%) with paired baseline and postinduction samples achieved negative minimal residual disease at a median sensitivity level of 6.73 x 10-6. Minimal residual disease negativity appeared comparable between patients assigned RAD and VRD.
“To the best of our knowledge, this is the first randomized controlled trial to compare two lenalidomide-based triplets prior to stem cell transplant,” Knop and colleagues wrote. “The endpoint was met with comparable postinduction complete remission rates for RAD and VRD. ... Tolerability was encouraging in both arms. Follow-up data is needed to analyze time-dependent endpoints.” – by Jennifer Southall
Reference:
Knop S, et al. Abstract 8001. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Knop reports honoraria from Bristol-Myers Squibb, Celgene, Janssen and Takeda; consultant or advisory roles with Bristol-Myers Squibb, Celgene and Takeda; and travel, accommodations or expenses from Celgene. Please see the abstract for a list of all other researchers’ relevant financial disclosures.