Second Primary Malignancies after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Abstract

Recent studies demonstrate an increased risk of second primary malignancies (SPM) in multiple myeloma (MM) patients on maintenance lenalidomide following autologous stem cell transplantation (ASCT). There may be other risk factors driving SPM post-ASCT in MM, so we explored this possibility through analysis of our large transplant database in conjunction with our long-term followup program. We conducted a retrospective cohort study of 841 consecutive MM patients who underwent ASCT from 1989–2009 at City of Hope, as well as a nested case-control analysis evaluating the role of all therapeutic exposures before, during and after ASCT. Median length of follow-up for the entire cohort was 3.4 years (range 0.3–19.9). Sixty cases with seventy SPM were identified. The overall cumulative incidence of SPM was 7.4% at five years and 15.9% at ten years if non-melanoma skin cancers (NMSCs) were included, and 5.3% at 5 years and 11.2% at 10 years if NMSCs were excluded. Multivariate analysis of the entire cohort revealed association of both older age (≥55yrs) (RR 2.3 p<0.004) and race (non-Hispanic white) (RR 2.4 p=0.01) with an increased risk of SPM. Furthermore, thalidomide exposure demonstrated a trend towards increased risk (OR=3.5, p=0.15); however, not enough patients were treated with lenalidomide to accurately assess the risk of this agent. Exclusion of NMSCs retained the association with these variables, but was accompanied with loss of statistical significance. This large single-institution analysis identified race and older age to be associated with increased risk of developing SPM. The trend toward increased risk with thalidomide exposure suggests a class effect from immunomodulatory drugs that may not be restricted to lenalidomide.

Second cancer risk in adults receiving autologous haematopoietic SCT for cancer: a population-based cohort study

“…4,[6][7][8]13,17 Other reports of second cancer rates after autologous HCT have not statistically compared the observed cancer rates with those of the general population. 10,11,18,19 Compared with the general population, we found an elevated second cancer risk in males, young adults and the earlier transplant eras. The high numbers of males transplanted for HL, NHL and testicular cancer may have influenced this finding to some extent, as these indications also had an increased second cancer risk.…”

“…NHL risk was significantly elevated within 1 year of HCT, but not thereafter. Three cancers were increased in risk only during certain time intervals from HCT; (5), rectum carcinoma (1), choriocarinoma (6), desmoid small cell tumour (2), ependymoma (2), esthesioneuroblastoma (1), germ cell tumour-unknown primary (7), germ cell tumourextragonadal (6), hepatoblastoma (1), intracranial germ cell tumour (4), lung carcinoma (12), mediastinum germ cell tumour (13), medulloblastoma (16), melanoma (1), merkel cell carcinoma (1), mixed germ cell tumour (1), mixed germ cell tumour-testis (15), myoepithelial sarcoma (1), nasopharyngeal carcinoma (1), neuroblastoma (5), neuroendocrine tumour (3), osteosarcoma (15), ovarian carcinoma (29), ovarian germ cell tumour (6), primitive neuroectodermal tumour (7), paragaglioma (1), pinealoblastoma (3), pulmonary germ cell tumour (1), rhabdomyosarcoma (27), seminoma (15), small cell tumour (4), soft tissue sarcoma (18), synovial sarcoma (2), teratoma (2), testicular germ cell tumour (13), thymic cancer (2), undifferentiated solid malignancy (1) and Wilm's tumour (3). c Other myeloid malignancies include: acute biphenotypic leukaemia (4), myelodysplasia (14) and chronic myelofibrosis (4).…”

The Shreveport Myeloma Experience: Survival, Risk Factors and Other Malignancies in the Age of Stem Cell Transplantation

“…In a review article which evaluates 5 decades, an incidence between 1.1 and 12.2% was reported [17], with most studies not mentioning a cumulative risk or the prognostic impact of having or developing an SMN. In two transplant studies that included younger patients without serious comorbidities, a cumulative incidence of 15.7% SMN after 10 years (from first diagnosis) [45] and 11.2% from the date of transplant [46] were reported. In the previously cited single-center study which included transplant and nontransplant patients and followed patients over more than 10 years, a cumulative SMN incidence of 11.6% at 10 years was estimated [40].…”

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

“…134 Retrospective reports from single institutions are difficult to interpret because of heterogeneity in patient populations. 135,136 A Center for International Blood and Marrow Transplant Research (CIBMTR) registry analysis did not demonstrate an increased risk in new malignancies with lenalidomide. 64 There are no data for more recently utilized maintenance therapies (e.g., Flt3 inhibitors).…”