Contributions
Abstract: EP1054
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Newly drugs access for MM treatment still a challenge in some countries. One of the most available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth and duration of the response. We hypothesized that the combination of Dara and CTd could be safe and allow deeper activity as an alternative protocol.
Aims
The primary endpoint was to evaluate the VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Secondary endpoints were the overall response rate during all treatment phases and minimal residual disease (MRD), based on the International Myeloma Working Group (IMWG) criteria that includes the next-generation flow (NGF) by the EuroFlow® and PET-CT and the safety profile.
Methods
This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. All pts received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis.
Results
The first pts was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 37 – 67 years), 19 (90%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and five (26%) pts needed plerixafor use. In an intention to treatment analysis, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 12 (70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Three pts died from infection, one before transplant because of Covid infection, on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 7), infection (n = 2), hypertension (n = 1) and rash (n = 1).
Conclusion
This is the first study that combined Dara with CTd as induction for TE NDMM pts. This present data has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPR after two consolidations cycles, and safety profile was acceptable. Clinical trial information: NCT03792620.
Keyword(s): Autologous bone marrow transplant, Minimal residual disease (MRD), Monoclonal antibody, Multiple myeloma
Abstract: EP1054
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Newly drugs access for MM treatment still a challenge in some countries. One of the most available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth and duration of the response. We hypothesized that the combination of Dara and CTd could be safe and allow deeper activity as an alternative protocol.
Aims
The primary endpoint was to evaluate the VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Secondary endpoints were the overall response rate during all treatment phases and minimal residual disease (MRD), based on the International Myeloma Working Group (IMWG) criteria that includes the next-generation flow (NGF) by the EuroFlow® and PET-CT and the safety profile.
Methods
This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. All pts received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis.
Results
The first pts was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 37 – 67 years), 19 (90%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and five (26%) pts needed plerixafor use. In an intention to treatment analysis, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 12 (70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Three pts died from infection, one before transplant because of Covid infection, on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 7), infection (n = 2), hypertension (n = 1) and rash (n = 1).
Conclusion
This is the first study that combined Dara with CTd as induction for TE NDMM pts. This present data has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPR after two consolidations cycles, and safety profile was acceptable. Clinical trial information: NCT03792620.
Keyword(s): Autologous bone marrow transplant, Minimal residual disease (MRD), Monoclonal antibody, Multiple myeloma