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Lenalidomide-Dexamethasone or Melphalan-Lenalidomide-Prednisone (MPR) or Cyclophosphamide-Prednisone-Lenalidomide (CPR) for Initial treatment of Real Life Elderly Patients with Newly Diagnosed Multiple Myeloma
Abstracts significant accumulation of the NuRD complex at MYC TSS after IMiDs exposure. Importantly, CHD4 silencing attenuated lenalidomide induced MYC transcriptional repression and cell death. In summary, our studies suggest that IKZF1 drives MYC expression in MM by regulating the activity of the IGH 3’ enhancer and preventing the repositioning of the NURD complex to its promoter.
5. Multiple Myeloma Therapy in Newly Diagnosed Patients excluding Transplantation
BP-041 Lenalidomide-Dexamethasone or Melphalan-Lenalidomide-Prednisone (MPR) or Cyclophosphamide-PrednisoneLenalidomide (CPR) for Initial treatment of Real Life Elderly Patients with Newly Diagnosed Multiple Myeloma V. Magarotto,1 S. Bringhen,1 P. Musto,2 G. Benevolo,2 A. Ledda,2 M. Genuardi,1 V. Pavone,2 F. Ciambelli,2 A.M. Cafro,2 E. Ponticelli,1 C. Cangialosi,2 M. Astolfi,1 S. Ronconi,2 D. Vincelli,2 G. Rossi,2 A.M. Liberati,2 M. Offidani,2 R. Hajek,3 M. Boccadoro,1 A. Palumbo1 1
Myeloma Unit, Division of Hematology, University of Torino, Torino,
Results: After a median follow-up of 43 months, the median PFS was 21 months with the doublet and 22 months with the triplet combinations (HR 0.923, p¼ 0.431). Median PFS was 24 months with MPR and 21 months with CPR (Rd vs MPR: HR 1.210, p¼0.113). Neutropenia was the most common grade 3 adverse event: the incidence was 25% in Rd, 64% in MPR and 29% in CPR patients (p<0.0001). Grade 3 non-hematologic adverse events were mainly infections (w 8%), constitutional (w 7%) and cardiac toxicities (w 5%) with no difference among the arms. In a post-hoc analysis, only fit patients benefited from a triplet combination. Median PFS was 22 months both in Rd and CPR and 30 months in MPR (Rd vs MPR HR¼1.457 p¼0.045). At least one hematologic events occurred in 29% of Rd, 75% of MPR and 34% of CPR fit patients (p<0.0001). Conclusion: In the real life elderly myeloma population, no difference in terms of PFS/OS was observed between doublet and triplet lenalidomide-containing regimens. Only fit patients benefited from a triplet combination (MPR) taking into account the highest hematologic toxicity.
BP-042 Age versus frailty: What should determine treatment choice in the elderly myeloma patients these days? S.G.R. Verelst, Y. van Norden, P. Sonneveld Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands; Clinical Trial Center e HOVON Data
Italy; Italian Multiple Myeloma Network, GIMEMA, Italy; Faculty of
Center, Erasmus University Medical Center, Rotterdam, The
Medicine, University of Ostrava and Department of Haematooncol-
Netherlands
2
3
ogy, University Hospital Ostrava, Ostrava, Czech Republic
Background: Lenalidomide-containing regimens improved outcome in elderly patients with newly diagnosed multiple myeloma (MM). A formal comparison between a doublet and a triplet Lenalidomide-containing regimens has not been performed yet. Patients and Methods: Patients with newly diagnosed MM not candidates for high-dose therapy plus stem-cell transplantation because of age ( 65 years) or coexisting comorbidities were considered eligible. A total of 662 MM patients were randomly assigned to received 928-day cycles of Rd (Lenalidomide 25 mg/day for 21 days and dexamethasone 40 mg on days 1,8,15,22 in patients 65-75 years old and 20 mg in those >75 years) or MPR (Lenalidomide 10 mg/day for 21 days; oral Melphalan 0.18 mg/Kg for 4 days in patients 65-75 years old and 0.13 mg/Kg in those >75 years; Prednisone 1.5 mg/Kg for 4 days) or CPR (Lenalidomide 25 mg/day for 21 days in patients 65-75 years old and 10 mg/day in those > 75 years; oral Cyclophosphamide 50 mg/day for 21 days in patients 65-75 years old and 50 mg every other day for 21 days in those >75 years; Prednisone 25 mg every other day). After induction, patients were randomized to receive maintenance treatment with Lenalidomide alone or in combination with Prednisone. The primary end-point was progression-free survival (PFS) in doublet (Rd) vs triplet (MPR+CPR) Lenalidomide-containing regimens.
The management of myeloma has largely changed since the introduction of immunomodatory drugs (iMIDs)and proteasomeinhibitors (PIs)in the last decade. Results on efficacy of different treatment result primarily from randomized controlled trials. Data on treatment effectiveness based on daily practice are sparse but necessary to provide complementary information. Within the available treatment options,choice seems to depend on frailty of the patient;primarily based on age, WHO-performance status and comorbidities. We collected data of 408 nontransplant eligible patients above 65-years diagnosed between January 2004 and December 2009 and determined treatment effectiveness as well as the impact of the 3 main choice definers of treatment selection and their impact on overall survival. 408 patients were included with a median follow up time of 45 months. Mean age at diagnosis was 76years, 53% were male, 59% had stage IIIA/B at diagnosis, 87% of patients had WHO 0-2. There was large diversity in number of pre-existing co-morbidities: ranging from 14% without any to 20% having 3 or more co-morbidities at diagnosis. Choice of treatment was significantly related with age and year of diagnosis. In the period 2004-2006, more patients of age 66-69 received an iMID-based first line than patients aged 70-79 and they, in turn, received more often an iMID-based as patients of 80+ years of age (40% versus 26% versus 12% respectively). Patients of 80+ years of age mainly received an alkylating based 1st line treatment (73%). In the period 2007-2009 an increase in iMID-based 1st line was observed
15th International Myeloma Workshop, September 23-26, 2015
- e69
5. Multiple Myeloma Therapy in Newly Diagnosed Patients excluding Transplantation
BP-041 Lenalidomide-Dexamethasone or Melphalan-Lenalidomide-Prednisone (MPR) or Cyclophosphamide-PrednisoneLenalidomide (CPR) for Initial treatment of Real Life Elderly Patients with Newly Diagnosed Multiple Myeloma V. Magarotto,1 S. Bringhen,1 P. Musto,2 G. Benevolo,2 A. Ledda,2 M. Genuardi,1 V. Pavone,2 F. Ciambelli,2 A.M. Cafro,2 E. Ponticelli,1 C. Cangialosi,2 M. Astolfi,1 S. Ronconi,2 D. Vincelli,2 G. Rossi,2 A.M. Liberati,2 M. Offidani,2 R. Hajek,3 M. Boccadoro,1 A. Palumbo1 1
Myeloma Unit, Division of Hematology, University of Torino, Torino,
Results: After a median follow-up of 43 months, the median PFS was 21 months with the doublet and 22 months with the triplet combinations (HR 0.923, p¼ 0.431). Median PFS was 24 months with MPR and 21 months with CPR (Rd vs MPR: HR 1.210, p¼0.113). Neutropenia was the most common grade 3 adverse event: the incidence was 25% in Rd, 64% in MPR and 29% in CPR patients (p<0.0001). Grade 3 non-hematologic adverse events were mainly infections (w 8%), constitutional (w 7%) and cardiac toxicities (w 5%) with no difference among the arms. In a post-hoc analysis, only fit patients benefited from a triplet combination. Median PFS was 22 months both in Rd and CPR and 30 months in MPR (Rd vs MPR HR¼1.457 p¼0.045). At least one hematologic events occurred in 29% of Rd, 75% of MPR and 34% of CPR fit patients (p<0.0001). Conclusion: In the real life elderly myeloma population, no difference in terms of PFS/OS was observed between doublet and triplet lenalidomide-containing regimens. Only fit patients benefited from a triplet combination (MPR) taking into account the highest hematologic toxicity.
BP-042 Age versus frailty: What should determine treatment choice in the elderly myeloma patients these days? S.G.R. Verelst, Y. van Norden, P. Sonneveld Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands; Clinical Trial Center e HOVON Data
Italy; Italian Multiple Myeloma Network, GIMEMA, Italy; Faculty of
Center, Erasmus University Medical Center, Rotterdam, The
Medicine, University of Ostrava and Department of Haematooncol-
Netherlands
2
3
ogy, University Hospital Ostrava, Ostrava, Czech Republic
Background: Lenalidomide-containing regimens improved outcome in elderly patients with newly diagnosed multiple myeloma (MM). A formal comparison between a doublet and a triplet Lenalidomide-containing regimens has not been performed yet. Patients and Methods: Patients with newly diagnosed MM not candidates for high-dose therapy plus stem-cell transplantation because of age ( 65 years) or coexisting comorbidities were considered eligible. A total of 662 MM patients were randomly assigned to received 928-day cycles of Rd (Lenalidomide 25 mg/day for 21 days and dexamethasone 40 mg on days 1,8,15,22 in patients 65-75 years old and 20 mg in those >75 years) or MPR (Lenalidomide 10 mg/day for 21 days; oral Melphalan 0.18 mg/Kg for 4 days in patients 65-75 years old and 0.13 mg/Kg in those >75 years; Prednisone 1.5 mg/Kg for 4 days) or CPR (Lenalidomide 25 mg/day for 21 days in patients 65-75 years old and 10 mg/day in those > 75 years; oral Cyclophosphamide 50 mg/day for 21 days in patients 65-75 years old and 50 mg every other day for 21 days in those >75 years; Prednisone 25 mg every other day). After induction, patients were randomized to receive maintenance treatment with Lenalidomide alone or in combination with Prednisone. The primary end-point was progression-free survival (PFS) in doublet (Rd) vs triplet (MPR+CPR) Lenalidomide-containing regimens.
The management of myeloma has largely changed since the introduction of immunomodatory drugs (iMIDs)and proteasomeinhibitors (PIs)in the last decade. Results on efficacy of different treatment result primarily from randomized controlled trials. Data on treatment effectiveness based on daily practice are sparse but necessary to provide complementary information. Within the available treatment options,choice seems to depend on frailty of the patient;primarily based on age, WHO-performance status and comorbidities. We collected data of 408 nontransplant eligible patients above 65-years diagnosed between January 2004 and December 2009 and determined treatment effectiveness as well as the impact of the 3 main choice definers of treatment selection and their impact on overall survival. 408 patients were included with a median follow up time of 45 months. Mean age at diagnosis was 76years, 53% were male, 59% had stage IIIA/B at diagnosis, 87% of patients had WHO 0-2. There was large diversity in number of pre-existing co-morbidities: ranging from 14% without any to 20% having 3 or more co-morbidities at diagnosis. Choice of treatment was significantly related with age and year of diagnosis. In the period 2004-2006, more patients of age 66-69 received an iMID-based first line than patients aged 70-79 and they, in turn, received more often an iMID-based as patients of 80+ years of age (40% versus 26% versus 12% respectively). Patients of 80+ years of age mainly received an alkylating based 1st line treatment (73%). In the period 2007-2009 an increase in iMID-based 1st line was observed
15th International Myeloma Workshop, September 23-26, 2015
- e69