Increased Risk of Second Primary Malignancy and Mortality at ten Years After Stem Cell Transplant for Multiple Myeloma: An Analysis of 14,532 Patients

Abstract

BackgroundThe landscape for patients with multiple myeloma has improved dramatically over the last 15 years. Immunomodulatory imide drugs (IMiDs) have shown great efficacy in both the setting of initial therapy and as maintenance after autologous stem cell transplant (ASCT). Concern has arisen, however, regarding the risk of second primary malignancies (SPMs) that appear to be associated with the use of IMiD agents. SPMs are a known sequela of multiple myeloma treatment, particularly as a consequence of maintenance lenalidomide status-post stem cell transplant (SCT). The benefit of SCT has become less clear with the utilization of newer, more effective initial therapies. ObjectivesTo determine the effect of SCT on SPM risk and overall survival in multiple myeloma patients at 5 and 10 years after treatment initiation. MethodsWe used TriNetX, a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 58 million patients in 49 large healthcare organizations. We created two patient cohorts who had all received treatment with thalidomide, lenalidomide, or pomalidomide. One cohort had received SCT while the other had not. Both cohorts were then analyzed for the development of all non-myeloma malignancies which occurred at least one year after initiation of treatment. ResultsAt 5 years, SPMs were 5.8% more likely in patients who received stem cell transplant (22.4% vs 16.6%, RR 0.741, p value <0.0001) but 5-year survival favored transplanted patients by 2.38% (64.85% vs 62.474%, p value 0.0044). 10-year survival favored patients who did not receive transplant by 1.44% (42.279% vs 40.838%, p value 0.0279). The Kaplan-Meier curves cross at year 6. ConclusionsIt has previously been shown that the use of alkylating agents in myeloma patients significantly increases the risk of SPM, but that difference had curiously not been shown to have a negative impact on survival. Our analysis shows that this negative survival impact does exist but requires six or more years of follow up to become evident. Recent analyses from studies using older regimens show no overall survival benefit from the use of stem cell transplant. As non-transplant regimens become more effective at producing minimal residual disease (MRD) negativity, it seems that transplantation for myeloma patients will soon be regarded as unnecessary or even detrimental.

Clinical Characteristics and Prognosis of Secondary Acute Lymphoblastic Leukemia in Patients with Multiple Myeloma during Long-Term Thalidomide Maintenance

“…Eleven patients tested negative for the BCR/ABL fusion gene (one case was not tested). Karyotyping was performed in six patients; only one patient had complex cytogenetics of 42, X,-Y,Del(1)(p12p31), +der (1), -10,-13,-16,-21 [ 1 ]/46,XY [ 2 ], and the other five patients had a normal karyotype. Six patients received induction therapy (vincristine + daunorubicin/idarubicin + prednisone ± pegaspargase); two of these patients subsequently underwent allogeneic hematopoietic stem cell transplantation; they were still disease-free survivors (DFS) until now.…”

“…The application of autologous hematopoietic stem cell transplantation (ASCT) and novel agents has significantly prolonged the survival of patients with multiple myeloma (MM), and secondary primary malignancies (SPM) have attracted increasing attention [ 1 , 2 , 3 ]. Large population-based studies showed that MM patients had a 26% increased risk of developing any SPM when compared to the general population [ 4 ].…”

Case report: pomalidomide as maintenance after salvage autologous stem cell transplantation in a patient with relapsed multiple myeloma

“…Так, в одном из популяционных исследова ний, охватывающих данные по 14,5 тыс. пациентов с ММ из 49 крупных медицинских центров США, при сроке наблюдения 5 лет вторые первичные злокачест венные опухоли были диагностированы у 22,4 % па циентов, получивших ВДХТ и аутоТГСК, и у 16,6 % па циентов, не получивших трансплантации (p <0,0001) [14]. У пациентов, проживших 10 лет и более, данная проблема возникла уже в 42,3 и 40,8 % случаев соот ветственно (p = 0,0279).…”

COVID-19-Related Trends and Characteristics of Type 2 Diabetes Mellitus and Metabolic Syndrome

“…Aggregate data from electronic health records (EHRs) were obtained from a subset of healthcare organizations (HCOs) that are associated with the TriNetX research network (TriNetX, Cambridge, MA) as described previously [12][13][14]. TriNetX is a global federated health research network that provides access to real-time EHR data, including demographics, diagnoses, laboratory results, and vital signs.…”