Hematology
Contributions
Type: Publication Only
Background
A three drug induction regimen followed by autologous transplantation is considered the best approach in multiple myeloma patients who can endure that procedure. Despite scarce evidence available, the combination of lenalidomide, bortezomib and weekly dexamethasone (VRd) has been widely adopted, probably due to more favourable toxicity profile as compared to bortezomib, thalidomide and dexamethasone
Aims
To review our center's experience in using VRd protocol and autologous transplantation as first line therapy in multiple myeloma patients
Methods
Multiple myeloma was diagnosed according to IMWG criteria, as well as response assessment. All patients fit enough to undergo transplantation were treated with VRd combination, as previously described by Richardson et al, except for weekly administration of 40 mg dexamethasone. Four cycles were initially scheduled, but two additional cycles could be administered if less than partial response was achieved. Only patients with creatinine clearance below 50 mL/min were excluded. At least partial response was required to proceed to transplantation. Postransplant consolidation with two cycles of bortezomib and dexamethasone was administered in case of partial response, as well as lenalidomide maintenance in order to achieve complete response
Results
From April 2011 to February 2014 a total of 19 patients were treated according to this protocol. Median age at diagnosis was 58 years, ranging 32 to 70. ISS score was 1 in 7/19, 2 in 7/19 and 3 in 5/19. One patient required second line therapy due to lack of response to VRd induction, but proceeded to transplant once a partial response to DT-PACE was achieved. Other patient did not receive transplantation because of significant cardiac amyloid deposition. Stem cell mobilization yielded enough cells for the procedure in all patients despite lenalidomide usage.
Responses after VRd induction therapy were complete response (CR) in 5/19, very good partial response (VGPR) in 4/19 and partial response (PR) in 10/19. A total of 18 transplantation procedures were performed, conditioned with melphalan 200 mg/m2 in 15 patients; the other 3 received 140 mg/m2 because of renal impairment (one patient) and poor tolerability to previous therapies (2 patients). Time to engraftment, infectious and non-infectious complications were similar to those previously reported. No deaths occurred during the procedure or immediately thereafter.
Response after transplantation was CR in 13/18 (strict in 11/13), VGPR in 2/18 and PR in 3/18. Transplant upgraded the response in 9 out of 18 patients (50%). Only three patients required posttransplant consolidation and four received lenalidomide maintenance.
After a median follow up of 28 months, a total of 11 patients (61%) have experienced relapse after a median of 18 months from start of treatment. Only 7 of them, (39%) have experienced clinical or paraprotein relapse requiring second line therapy. Median progression free survival is 22 months. No second neoplasms have been detected so far
Summary
VRd induction followed by autologous transplantation is a safe and effective therapy for newly diagnosed multiple myeloma. Half of the patients upgraded their response after transplantation, making it an essential part of therapy. Despite excellent responses achieved, relapse is still the main cause of failure
Keyword(s): Myeloma, Transplant
Type: Publication Only
Background
A three drug induction regimen followed by autologous transplantation is considered the best approach in multiple myeloma patients who can endure that procedure. Despite scarce evidence available, the combination of lenalidomide, bortezomib and weekly dexamethasone (VRd) has been widely adopted, probably due to more favourable toxicity profile as compared to bortezomib, thalidomide and dexamethasone
Aims
To review our center's experience in using VRd protocol and autologous transplantation as first line therapy in multiple myeloma patients
Methods
Multiple myeloma was diagnosed according to IMWG criteria, as well as response assessment. All patients fit enough to undergo transplantation were treated with VRd combination, as previously described by Richardson et al, except for weekly administration of 40 mg dexamethasone. Four cycles were initially scheduled, but two additional cycles could be administered if less than partial response was achieved. Only patients with creatinine clearance below 50 mL/min were excluded. At least partial response was required to proceed to transplantation. Postransplant consolidation with two cycles of bortezomib and dexamethasone was administered in case of partial response, as well as lenalidomide maintenance in order to achieve complete response
Results
From April 2011 to February 2014 a total of 19 patients were treated according to this protocol. Median age at diagnosis was 58 years, ranging 32 to 70. ISS score was 1 in 7/19, 2 in 7/19 and 3 in 5/19. One patient required second line therapy due to lack of response to VRd induction, but proceeded to transplant once a partial response to DT-PACE was achieved. Other patient did not receive transplantation because of significant cardiac amyloid deposition. Stem cell mobilization yielded enough cells for the procedure in all patients despite lenalidomide usage.
Responses after VRd induction therapy were complete response (CR) in 5/19, very good partial response (VGPR) in 4/19 and partial response (PR) in 10/19. A total of 18 transplantation procedures were performed, conditioned with melphalan 200 mg/m2 in 15 patients; the other 3 received 140 mg/m2 because of renal impairment (one patient) and poor tolerability to previous therapies (2 patients). Time to engraftment, infectious and non-infectious complications were similar to those previously reported. No deaths occurred during the procedure or immediately thereafter.
Response after transplantation was CR in 13/18 (strict in 11/13), VGPR in 2/18 and PR in 3/18. Transplant upgraded the response in 9 out of 18 patients (50%). Only three patients required posttransplant consolidation and four received lenalidomide maintenance.
After a median follow up of 28 months, a total of 11 patients (61%) have experienced relapse after a median of 18 months from start of treatment. Only 7 of them, (39%) have experienced clinical or paraprotein relapse requiring second line therapy. Median progression free survival is 22 months. No second neoplasms have been detected so far
Summary
VRd induction followed by autologous transplantation is a safe and effective therapy for newly diagnosed multiple myeloma. Half of the patients upgraded their response after transplantation, making it an essential part of therapy. Despite excellent responses achieved, relapse is still the main cause of failure
Keyword(s): Myeloma, Transplant