Autologous Stem Cell Transplantation in Newly Diagnosed Elderly Multiple Myeloma Patients: A Single Centre Experience

Introduction: Multiple myeloma (MM) is a plasma cell malignancy that affects older adults with a median age at diagnosis of 70 years. Autologous stem cell transplantation (ASCT) in combination with novel agents is the standard of care for young patients with newly diagnosed MM. The safety and efficacy of High Dose Therapy (HDT) as upfront treatment in elderly patients remain still uncertain, because elderly patients age are frequently associated with increased comorbidities, compromised physical conditions and a suspected increased treatment-related toxicity. In our centre we analyzed the treatment-related toxicities and the outcome in a homogeneous cohort of newly diagnosed elderly MM patients treated with HDT approach.

Methods: we retrospectively evaluated 16 newly diagnosed elderly MM patients, according to International Myeloma Working Group (IMWG). All of them were fit/low-risk according to revised Myeloma Comorbidity Index. Median age at diagnosis was 66 years (range 65-68 years), and at transplantation 67 years (range 65-69). The MM immunoglobulin subtypes were: 9 IgG k (56.25%); 1 IgG l (6.25%), 1 IgA k (6.25%), 1 IgA l (6.25%), 1 light chain l (6.25%) and 3 light chain k (18,75%). In 5 patients we detected extramedullary plasmocitoma. The revised International Staging System (R-ISS) stage was: I in 8 patients (50%), II in 5 cases (31.25%) and III in 3 patients (18.75%). FISH analysis was performed at diagnosis in all patients, we found standard-risk in 10 patients (62.5%), intermediate-risk in 3 cases (18.75%) and high-risk in 3 cases (18.75%). All patients had a normal renal function. Immunoparesis occurred in 13 patients (81.25%) at diagnosis. The induction therapy was bortezomib-based in association with dexamethasone (VD) with or without thalidomide (VTD). Radiotherapy was performed in extramedullary disease. The mobilization regimen included cyclophosphamide at different doses (2 to 4 gr/mq) followed by G-CSF. The conditioning regimen consisted of melphalan 140 mg/mq or 200 mg/mq given over two days. A short 2-month consolidation phase bortezomib-based was given three months post ASCT.

Results: As induction therapy 8 patients (50%) received VD, the other 50% VDT. Five patients (31.25%) underwent radiotherapy. A median of 12.6x10⁶/kg CD34+cells were collected after cyclophosphamide treatment. Melphalan 140 mg/mq conditioning regimen was administered in 10 patients (62.5%) and 200 mg/mq in 6 patients (37.5%). Seven patients (43.75%) received consolidation treatment. The overall response rate (ORR) to induction therapy (≥ PR) was 93.75% including 2 CR (12.5%), 7 VGPR (43.75%) and 6 PR (37.5%). The ORR after ASCT increased to 100%: 3 CR (18.75%), 11 VGPR (68.75%) and 2 PR (12.5%). Immunoglobulin recovery 1 year after ASCT occurred in 9 patients (69.23%) out of 13 with immunoparesis. Median time to neutrophil and platelet engraftment was 10 days (range 6-18 days). No significant difference in toxicity was found among the two groups (MEL140 vs MEL200). The non-hematological toxicities after ASCT (G3-G4) included infections in 8 patients (50%), gastrointestinal disorders in 8 cases (50%), and nervous system disorders (G3) in 7 cases (43.75 %). In 1 patient we observed cardiac toxicity (G2). The day-100 post ASCT treatment-related mortality (TRM) was 0%. During follow up we reported secondary malignancies in 2 cases (12.5%) and one therapy-related myeloid neoplasm (t-MDS) (6.25%). After a median follow up of 59.5 months (range 21-73.3 months) the median PFS was 16.7 months in MEL140 group vs 28.3 months in MEL200. The difference among these two groups was statistically significant (p= 0.04).

Conclusions:our results suggest that ASCT is a safe and well-tolerated procedure in our small cohort of elderly and fit patients. We detected among the two regimens (MEL140 and MEL200) a similar profile of toxicities. The dose of Melphalan (MEL200) impacted on the duration of response and the PFS resulted significantly higher. According to literature we confirm that an accurate assessment of elderly patients performance status, comorbidities and myeloma characteristics (by means of R-MCI) at diagnosis can help to develop individualized risk-adapted treatment strategies to improve the outcome, especially in elderly MM patients even in the era of new and highly effective drugs.