High dose chemotherapy and autologous stem cell transplantation in Multiple Myeloma patients over 70 years: “GIMEMA Working Group Lazio experience

Abstract

Introduction: Multiple Myeloma (MM) mostly affects elderly patients (median age of 69 years). The standard regimens and the development of novel therapies followed by autologous stem cell transplantation (ASCT) improved clinical outcomes.. In fact, treatments including single or double ASCT are considered, at this time, the best treatment option for MM patients. Elderly patients, older than 70 years, however, are usually rarely eligible to these therapies, since they are usually characterized, at diagnosis, by higher incidence of comorbidities, frailty and organ dysfunction... Aim of our study was to retrospectively evaluate the incidence of ASCT performed in patients between 70 and 75 years, among the MM GIMEMA Working Group Lazio, to describe the baseline patient’s characteristics and to evaluate the ASCT outcome. Methods: We retrospectively analysed among 813 MM patients undergoing ASCT in 7 centers of GIMEMA Group Lazio between 1999 and 2019, those who underwent ASCT. Generally, patients have been considered eligible for ASCT by the treating physicians according to age, performance status and organ function. Therefore, we analysed criteria adopted for including these patients in the ASCT program (absence of comorbidities, biological vs chronological age, etc.) and treatment related toxicity (TRM) occurring during and following the ASCT, previous adopted regimens, and dose of Melphalan used as condition therapy and days of engrafment. Results: The incidence of MM patients over 70 years underwent to ASCT , in our group, was 1.5% (13/813). At diagnosis median age was 71 years, (range 70-74); M/F:8/5, ISS stage was: I (n=7), II (n=2) and III (n=2) and unknown in 2 pts. The comorbidities were: arterial hypertension (n=4), cardiomyopathy (n=1), hepatitis C (n=1). Several different induction treatments were used, either based on Bortezomib (n=10), immunomodulatory drugs (n=1) and chemotherapy (n=1). During induction therapy, neuropathy was reported in 7 out of 13 cases. Very good partial response (VGPR) was observed in 7 pts partial response (PR) in 2, complete response (CR) in 3, and not evaluated in 1 pts. ASCT was performed using a reduced Melphalan dose of 140 mg/m2 (MEL140) in 10/13 pts, MEL100 in 2/13 and standard dose MEL200 in 1/13pts. The median time of engrafment was 11 days (range 10-14) without any difference among the 3 different group of MEL dose. The response evaluated at 100 days from the ASCT was: VGPR (n=8), CR (n=3), PR (n=1) and one pts is now in development. Side effects after ASCT were: mucositis (n=5), vomiting (n=3), diarrhea (n=3), sepsis (n=1). Maintenance therapy, Lenalidomide in 5 pts and Interferon in 1 pts, was started after ASCT. Two progressions were observed after 5.5 and 7.2 years from ASCT respectively. After a median follow-up of 24.8 months (range: 20-178) 12 pts are alive and 1 pts died after disease progression. Conclusions: Despite the small number of our patient, our findings support the idea that ASCT can be safely administered as first-line also in well-selected patients ≥ 70 years old.