SAN DIEGO — Long-term follow-up from the only randomized controlled trial to compare salvage autologous stem cell transplant with a standard two-drug regimen in patients with relapsed or refractory multiple myeloma found no benefit to salvage transplant.
Patients receiving a second, salvage-autologous stem cell transplant alongside lenalidomide-dexamethasone maintenance therapy did not demonstrate improved progression-free survival (PFS) or overall survival compared with patients who continued the two-drug regimen without salvage transplant, according to research presented at the American Society of Hematology (ASH) annual meeting.
The primary phase 3 analysis, published in 2021, showed no survival benefit following salvage transplant at the time of relapse, though it only followed patients for a median of 37 months.
However, because a significant fraction of patients in the transplant arm — about 29% — did not undergo the planned salvage transplant before dropping out of the study, the researchers performed further analyses that "suggested a survival benefit in patients who actually received the transplant," first author Marc-Andrea Baertsch, MD, of the German Cancer Research Center and University Hospital Heidelberg, reported at ASH.
Now, the latest analysis, which followed patients for a median of 99 months (8.25 years) , confirmed the initial 2021 findings, Baertsch explained.
"The writing on the wall is clear: don't repeat a transplant at the time of relapse for those who have already gotten a transplant," commented Manni Mohyuddin, MD, of the University of Utah in Salt Lake City, who was not involved in the research. Mohyuddin added, however, that this finding doesn't apply to those who haven't yet gotten a transplant. "Data from other trials suggests a role of transplant in this situation depending on the unique circumstances."
The current trial included 282 adult patients, aged 75 years or younger, with relapsed or refractory multiple myeloma. Between 2010 and 2016, patients in the intention-to-treat analysis (n = 277) were randomized to lenalidomide-dexamethasone reinduction and maintenance, along with salvage high-dose chemotherapy with melphalan and autologous stem cell transplantation (n = 139) or just continuous lenalidomide-dexamethasone until progression (n = 138).
Patients in both arms received three cycles of lenalidomide-dexamethasone up front: 25 mg of lenalidomide on days 1 through 21, and 40 mg of dexamethasone on days 1, 8, 15, and 22 in 4-week cycles. Those in the salvage transplant arm then received high-dose chemotherapy with 200 mg/m2 of melphalan followed by transplant and 10 mg of lenalidomide maintenance therapy daily, while those in the control arm continued with receiving lenalidomide-dexamethasone.
All patients had received one to three prior lines of therapy, had good performance status, and had a time-to-disease-progression of at least 12 months after frontline autologous stem cell transplant.
In the primary 2021 study, patients in the salvage transplant group did not demonstrate a survival benefit (hazard ratio [HR] for PFS, 0.87; HR for overall survival, 0.81).
In the latest analysis, no survival benefit emerged after following patients for a median of about 8 years. Patients in the salvage transplant arm had a median PFS of 20.5 months vs 19.3 months in the continuous therapy arms (HR, 0.98; 95% CI, 0.76 - 1.27; P = .9). Median overall survival was 67.1 months in the salvage transplant arm and 62.7 months in the continuous treatment arm (HR, 0.89; 95% CI, 0.66 - 1.20; P = .44).
Time to first progression after frontline transplant was associated with a PFS benefit but did not predict an overall survival benefit, Baertsch noted.
When evaluating outcomes from the time of salvage transplant to account for the high number of dropouts, the PFS and overall survival findings held. Patients who received salvage transplant did not experience significantly improved PFS (HR, 0.91) or overall survival (76.3 months in the salvage group vs 65.9 months in the continuous treatment arm; HR, 0.80).
The lack of PFS and overall survival benefit occurred across all myeloma subgroups, Baertsch said.
Overall, the results indicate that " a repeat transplant at the time of relapse for patients who had already gotten a transplant previously was no better than continuing a two-drug regimen," Mohyuddin said.
However, he noted, "a lot has changed for myeloma care" since this trial was initially conducted. "We now have better regimens available that do not involve a transplant. If a repeat transplant couldn't beat a two-drug regimen, it surely cannot beat a three drug or four drug regimen."
Baertsch reported no disclosures.
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on Twitter: @SW_MedReporter.
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