Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM) Patients over Age 70.
Authors: Borgono Carla , Trieu Young , Xu Wei , Pendergrast Jacob , Reece Donna , Trudel Suzanne , Mikhael Joseph , Kukreti Vishal , Chen Christine I. 
Published: October 2019

Introduction: MM is a disease of the elderly with a median age of 65 years at diagnosis. Melphalan-based ASCT is standard therapy for younger (<60–65 years) MM patients (pts). However, limited data are available on the efficacy of ASCT in pts over age 70 with concerns of excess toxicity and transplant-related mortality (TRM).

Methods: In this retrospective study, we examined the feasibility of ASCT in 33 MM pts ≥ age 70 (median age 71 yrs; range 70–74) who underwent this procedure at Princess Margaret Hospital from October 2000 to August 2006. As per institutional standard, all pts received 3–6 cycles of high-dose dexamethasone (DEX)-based induction therapy (VAD or DEX-alone) and underwent standard stem cell mobilization with cyclophosphamide 2.5g/m2 and GCSF 10mg/kg/day. Routine ciprofloxacin prophylaxis and GCSF use (from day 7) were used during the transplant process.

Results: Nineteen pts(58%) were male. Baseline lab values (at time of transplant) were as follows: median hemoglobin 106g/L(range 83–144), WBC 6.7x109/L(range 1.9–11.9), platelets 191x109/L(range 103–319) and creatinine 69mmol/L(range 43–191mmol/L). Pre-transplant ECOG was 0–2 for all pts. Co-morbidities were reported for 29 pts(88%) and included prior solid tumours(18%) and cardiac disorders (arrhythmia, infarction) (15%). MM isotypes included: IgG 22(67%), IgA 6(18%), IgD 1 (3%), biphenotypic IgA/IgM 1(3%), nonsecretory 3(9%). A median of 9.1x106 CD34 cells/kg body weight (range 2.2–25.4x106cells/kg) were collected. Median time to engraftment of neutrophils and platelets was 12 days(range 9–13) and 11 days(range 8–15), respectively. Median duration of hospitalization was 15 days (range 12–40). Transfusion support (red cells and/or platelets) from time of stem cell collection to day 100 post-ASCT was required in 30/33 (91%) pts. Responses (all PR) were achieved in 24/27 pts (89%) with measurable disease. At a median follow-up of 18.3 months (mos) post-transplant, 16 pts (50%) relapsed and 14 (44%) died (follow-up data available in 32 pts). Median progression-free survival (PFS) was 23.3 mos; median overall survival (OS) was 41.2 mos from transplant. Three-year PFS and OS were 70% and 38%, respectively. TRM was 0%. Most common toxicities included: fever(67%), mucositis(46%), infections(46%), diarrhea(42%) and cardiac arrhythmias(18.2%) [all CTC grade 1–2]. Grade 3–4 toxicities were uncommon and included: myocardial infarction(6%), diarrhea(3%) and mucositis(3%). Overall, cardiac toxicities were more frequent than expected. The relationship between pre-ASCT parameters (e.g. isotype, lab values at transplant, co-morbidities and number of stem cells collected) and outcomes (e.g. PFS, OS, grade 3–4 toxicities) were assessed by univariate analysis. A higher number of CD34 cells harvested correlated with shorter days to neutrophil and platelet engraftment (p<0.0008) and prolonged PFS (p=0.043). Pts with IgA vs. IgG or other subtypes had a shortened PFS post-transplant (p=0.003). No significant predictors of OS or grade 3–4 toxicities were identified.

Summary: Our preliminary data suggest that ASCT is feasible and generally well-tolerated in selected elderly (≥ 70 yrs) MM pts. Although toxicities, in particular cardiac, appear more common in this population, PFS and OS are comparable to that in younger pts and TRM was not elevated. We support consideration of very elderly pts for ASCT but encourage careful co-morbidity screening pre-transplant.