Timing, patterns of relapse predict survival after HSCT for multiple myeloma
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ORLANDO — Time to relapse appeared prognostic for survival among individuals with multiple myeloma who underwent CD34 positive-selected allogeneic hematopoietic stem cell transplantation, according to study results presented at TCT | Transplantation & Cellular Therapy Meetings.
Very early relapse appeared linked to greater chemoresistance and poor prognosis, whereas those who relapsed more than 24 months after allogeneic HSCT survived for a median 6 years after transplant. In addition, relapse with extramedullary disease and lack of donor lymphocyte infusion also predicted worse outcomes.
“When people think about allogeneic transplant for multiple myeloma, it’s typically for very high-risk patients. The fact that some of these patients can do really well and live as long as they did even after they relapsed after transplant is amazing,” Alexandra Gomez-Arteaga, MD, of the adult bone marrow transplant service in the department of medicine at Memorial Sloan Kettering Cancer Center, told Healio.
Allogeneic HSCT is a potentially curative strategy for patients with high-risk multiple myeloma.
Relapse is the primary cause of treatment failure; however, predictors for post-relapse survival after transplantation have not been established.
Gomez-Arteaga and colleagues hypothesized that time to relapse and patterns of relapse could predict post-relapse survival.
Researchers reviewed data of 115 patients with multiple myeloma who underwent CD34 positive-selected allogeneic HSCT at Memorial Sloan Kettering — either on protocol or off study — between January 2010 and December 2017 and progressed after transplantation.
All patients received conditioning with busulfan (0.8 mg/kg for 10 doses), melphalan (70 mg/m2 for two doses) and fludarabine (25 mg/m2 for five doses).
The analysis included the 60 transplanted patients (median age, 56 years; range, 35-66) who relapsed. The majority were men (62%) and had high-risk cytogenetics (82%). All patients had Karnofsky Performance Status scores of 80 or higher, and 52% had scores of 90 or higher.
Patients had received a median four lines of therapy (range, 1-10) prior to HSCT, and most (88%) had achieved at least partial response to allogeneic HSCT.
All patients had undergone at least one autologous HSCT. More than one-third (38%) had received planned or preemptive post-HSCT therapy; of these, 13 had received donor lymphocyte infusion and 10 had received other strategies.
Gomez-Arteaga and colleagues classified relapses as very early (less than 6 months; 28%), early (6-24 months; 50%) or late (more than 24 months; 22%).
Approximately one-quarter (27%) of patients presented at relapse with extramedullary disease.
Median post-relapse OS differed significantly based on relapse timing (very early, 4 months; early, 17 months; late, 72 months; P = .002). These results suggested different underlying disease biology and/or host/donor characteristics, Gomez-Arteaga and colleagues concluded.
Univariate analysis revealed several factors prognostic for shorter post-relapse OS, including age 55 years or older, relapse with extramedullary disease, lower Karnofsky Performance Status score, less than partial response to HSCT, less than partial response by day 100 and no maintenance. Researchers reported no significant difference in post-relapse OS based on number of lines of therapy, high-risk cytogenetics or era of allogeneic HSCT.
Multivariate analysis adjusted for age and sex identified four factors predictive of shorter post-relapse OS: very early relapse (HR = 4.4; 95% CI, 1.4-13.5), early relapse (HR = 2.5; 95% CI, 1.4-13.5), relapse with extramedullary disease (HR = 5.2; 95% CI, 2.1-12.9) and lack of donor lymphocyte infusion as planned post-transplantation therapy (HR for infusion vs. no infusion = 0.11; 95% CI, 0.01-0.9).
“The take-home message is that allogeneic stem cell transplantation will still be a valuable option for patients with multiple myeloma, and it still has a role in treatment,” Gomez-Arteaga told Healio. “We don’t know how it will be affected by other therapies, such as chimeric antigen receptor T-cell therapies, but at some point we will have to create studies to define the role of allogeneic transplant. ... We also want to characterize how these patients are relapsing — such as human leukocyte antigen loss or some other mechanism — so we can strive to target those mechanisms.” – by Mark Leiser
Reference: Gomez-Arteaga A, et al. Abstract 25. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosure: Gomez-Arteaga reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
Back to TopYago L. Nieto, MD
That was a very interesting paper. They do many more allogeneic transplants for myeloma at Memorial Sloan Kettering Cancer Center than they do at most other centers, including mine.
It is very intriguing that patients who received preemptive donor lymphocyte infusion after allogeneic transplant and then relapsed still survived much longer after relapse than other patients. Those who never received donor lymphocyte infusion before relapse fared much worse, and the gap in the curves was very striking.
That leads to a lot of intriguing biological hypotheses as to what the timing of the graft-versus-myeloma effect may have been for those patients. After allogeneic transplant, it can take 3 to 4 months for the graft-versus-tumor effect to set in. One might speculate that patients got donor lymphocyte infusion but the tumor relapsed before the donor lymphocytes had enough time to start acting. Then it might be that some response to those same donor lymphocytes following relapse might be responsible for the improved survival. That was a very intriguing observation.
Nonrelapse mortality for this procedure is around 26%. That is quite high. Investigators in this study used a T-cell-depleted approach, which — in theory — prevents GVHD at the expense, of course, of lower graft-versus-tumor effect. If allogeneic transplant for myeloma is going to settle in as a therapeutic modality, even for a specific and highly selected group of patients, we need to do better at decreasing treatment-related mortality.
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