Contributions
Abstract: PB2225
Type: Publication Only
Background
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) is the standard of care for young newly diagnosed MM patients. The safety and efficacy of High Dose Therapy (HDT) as upfront treatment in elderly patients remain still uncertain, because elderly age is frequently associated with increased comorbidities and suspected increased treatment-related toxicity.
Aims
In our centre we analyzed the outcome and toxicities in a homogeneous cohort of newly diagnosed elderly MM patients treated with HDT approach.
Methods
We retrospectively evaluated 24 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 (R-MCI). Median age at diagnosis was 66 years (range 65-68 years), and at transplantation 66.5 years (range 65-69). The revised International Staging System (R-ISS) stage was: I in 12 patients (50%), II in 8 cases (33%), III in 3 patients (12.5%) and unknown in 1 patient (4%). FISH analysis were performed at diagnosis in all patients, and we found standard-risk in 11 patients (46%), intermediate-risk in 4 cases (16%), high-risk in 3 cases (12.5%) and not assessable in 6 patients. Immunoparesis occurred in 19 patients (80%) at diagnosis. The induction therapy was bortezomib-based in association with dexamethasone (VD) with or without thalidomide (VTD). The mobilization regimen included cyclophosphamide followed by G-CSF. The conditioning regimen consisted of melphalan 140 mg/mq or 200 mg/mq given over two days.
Results
As induction therapy 10 patients (41.5%) received VD, 11 patients (46%) VDT and 3 patients received bortezomib-based therapy plus infusional chemotherapy regimens (12.5%). Melphalan 140 mg/mq conditioning regimen was administered in 14 patients (60%) and 200 mg/mq in 10 patients (40%). The overall response rate (ORR) to induction therapy (≥PR) was 91.6% including 5 CR (21%), 10 VGPR (41.5%), 7 PR (29%) and 2 SD (8.5%). The ORR after ASCT increased to 96%: 5 CR (21%), 14 VGPR (58.5%), 4 PR (16.5%) with 1 death. Immunoglobulin recovery 1 year after ASCT occurred in 15 patients (62.3%) out of 19 with immunoparesis at diagnosis. 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 12 patients (50%) and gastrointestinal disorders in 10 cases (41.5%). In 1 patient we observed cardiac toxicity (G2). The day-100 post ASCT treatment-related mortality (TRM) was 4% (1 patients died after conditioning regimen). During follow up we reported secondary malignancies in 2 cases (8%) and one therapy-related myeloid neoplasm (t-MDS). The mean PFS was 30 months in MEL140 group vs 53 months in MEL200 (p= 0.11), no significant difference in OS was observed (p =0.3).
Conclusion
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) seems to impact on the duration of response, with a statistically significant trend in PFS. We confirm that an accurate assessment of elderly patients performance status and comorbidities at diagnosis, can help to develop risk-adapted treatment strategies to improve outcome, in elderly MM patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Melphalan, Myeloma, toxicity, Transplant
Abstract: PB2225
Type: Publication Only
Background
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) is the standard of care for young newly diagnosed MM patients. The safety and efficacy of High Dose Therapy (HDT) as upfront treatment in elderly patients remain still uncertain, because elderly age is frequently associated with increased comorbidities and suspected increased treatment-related toxicity.
Aims
In our centre we analyzed the outcome and toxicities in a homogeneous cohort of newly diagnosed elderly MM patients treated with HDT approach.
Methods
We retrospectively evaluated 24 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 (R-MCI). Median age at diagnosis was 66 years (range 65-68 years), and at transplantation 66.5 years (range 65-69). The revised International Staging System (R-ISS) stage was: I in 12 patients (50%), II in 8 cases (33%), III in 3 patients (12.5%) and unknown in 1 patient (4%). FISH analysis were performed at diagnosis in all patients, and we found standard-risk in 11 patients (46%), intermediate-risk in 4 cases (16%), high-risk in 3 cases (12.5%) and not assessable in 6 patients. Immunoparesis occurred in 19 patients (80%) at diagnosis. The induction therapy was bortezomib-based in association with dexamethasone (VD) with or without thalidomide (VTD). The mobilization regimen included cyclophosphamide followed by G-CSF. The conditioning regimen consisted of melphalan 140 mg/mq or 200 mg/mq given over two days.
Results
As induction therapy 10 patients (41.5%) received VD, 11 patients (46%) VDT and 3 patients received bortezomib-based therapy plus infusional chemotherapy regimens (12.5%). Melphalan 140 mg/mq conditioning regimen was administered in 14 patients (60%) and 200 mg/mq in 10 patients (40%). The overall response rate (ORR) to induction therapy (≥PR) was 91.6% including 5 CR (21%), 10 VGPR (41.5%), 7 PR (29%) and 2 SD (8.5%). The ORR after ASCT increased to 96%: 5 CR (21%), 14 VGPR (58.5%), 4 PR (16.5%) with 1 death. Immunoglobulin recovery 1 year after ASCT occurred in 15 patients (62.3%) out of 19 with immunoparesis at diagnosis. 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 12 patients (50%) and gastrointestinal disorders in 10 cases (41.5%). In 1 patient we observed cardiac toxicity (G2). The day-100 post ASCT treatment-related mortality (TRM) was 4% (1 patients died after conditioning regimen). During follow up we reported secondary malignancies in 2 cases (8%) and one therapy-related myeloid neoplasm (t-MDS). The mean PFS was 30 months in MEL140 group vs 53 months in MEL200 (p= 0.11), no significant difference in OS was observed (p =0.3).
Conclusion
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) seems to impact on the duration of response, with a statistically significant trend in PFS. We confirm that an accurate assessment of elderly patients performance status and comorbidities at diagnosis, can help to develop risk-adapted treatment strategies to improve outcome, in elderly MM patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Melphalan, Myeloma, toxicity, Transplant