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Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx

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Kunal Chhattani

This document discusses the history and current state of treatment for multiple myeloma. It begins with a brief history of treatments from the 1960s including melphalan and prednisone and the introduction of autologous stem cell transplantation in the 1980s. It then focuses on the approval and mechanisms of proteasome inhibitors (PIs) including carfilzomib. Several studies are summarized that show carfilzomib based regimens achieving high rates of stringent complete response and minimal residual disease negativity in both relapsed and newly diagnosed multiple myeloma patients including those with high-risk disease. While cardiac toxicity has been a concern, it is reported to occur in only a low number of patients.

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CARFILZOMIB BASED TREATMENT IN NEWLY DIAGNOSED MULTIPLE MYELOMA Dr Kunal Chhattani, Clinical Hematologist, Nagpur
HISTORY OF MULTIPLE MYELOMA TREATMENT In the 1960s,oral melphalan, an alkylating agent, in combination with prednisone was considered the frontline treatment for MM -Hoogstraten, B.; Sheehe, P.R.; Cuttner, J.; Cooper, T.; Kyle, R.A.; Oberfield, R.A.; Townsend, S.R.; Harley, J.B.; Hayes, D.M.; Costa, G.; et al. Melphalan in multiple myeloma. Blood 1967, 30, 7483
In the 1980s, autologous stem cell transplantation (ASCT) followed by a high dose of therapy was introduced. -Osserman, E.F.; DiRe, L.B.; DiRe, J.; Sherman, W.H.; Hersman, J.A.; Storb, R. Identical twin marrow transplantation in multiple myeloma. Acta Haematol. 1982, 68, 215223.
FDA APPROVALS OF PIS -Past, Present, and a Glance into the Future of Multiple Myeloma Treatment Weam Othman Elbezanti et al 2023
MECHANISM OF ACTION OF PIS Past, Present, and a Glance into the Future of Multiple Myeloma Treatment. Weam Othman Elbezanti et.al, March 23.
CURRENT STANDARD OF CARE FOR NDMM RVD TRIPLET, SWOG S0777 TRIAL
RVD APPROVAL FRONTLINE- SWOG S0777 TRIAL
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
CARFILZOMIB IN RELAPSED MYELOMA- ASPIRE TRIAL,2015
CARFILZOMIB IN RELAPSED MYELOMA- ASPIRE TRIAL
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
CARFILZOMIB IN TREATMENT NAVE NDMM PATIENTS
JAKUBOWIAK ET AL 2012
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
33% of patients had Unfavourable Cytogenetics 45% sCR rate after 4 cycles. 24 months PFS- 92%.
JASEILEC ET AL , 2020
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
60 months PFS- 72% and OS- 84% High risk cytogenetics- 57% and 72% respectively MRD negativity -60% after 8 cycles Grade III and IV cardiac events 3%
ROUSELL ET. AL. 2021 ASH
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Median PFS -56months and median OS not reached High rates of MRD negativity even after induction
FORTE TRIAL 2018
474 NDMM pts were randomized (KRd_ASCT, n=158; KRd12, n=157; KCd_ASCT, n=159).
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
KRD ASCT > KRD > KCD ASCT
RVD Vs KRD Head to head- Endurance trial 2020
ENDURANCE TRIAL 2020
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx
No significant difference between KRD and RVD without HSCT. Trial excluded High risk Patients
LIST OF STUDIES DOCUMENTING MRD Current Main Topics in Multiple Myeloma
FOR CARFILZOMIB Deeper and quicker responses- high rate of sCR rates post induction High rate of MRD negativity in trials Activity against High risk myeloma Cardiac toxicity , though of caution, is seen in low number of patients. Deeper responses can be cost effective in long run.
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Carfilzomib In Newly Diagnosed Multiple Myeloma.pptx

  • 1. CARFILZOMIB BASED TREATMENT IN NEWLY DIAGNOSED MULTIPLE MYELOMA Dr Kunal Chhattani, Clinical Hematologist, Nagpur
  • 2. HISTORY OF MULTIPLE MYELOMA TREATMENT In the 1960s,oral melphalan, an alkylating agent, in combination with prednisone was considered the frontline treatment for MM -Hoogstraten, B.; Sheehe, P.R.; Cuttner, J.; Cooper, T.; Kyle, R.A.; Oberfield, R.A.; Townsend, S.R.; Harley, J.B.; Hayes, D.M.; Costa, G.; et al. Melphalan in multiple myeloma. Blood 1967, 30, 7483
  • 3. In the 1980s, autologous stem cell transplantation (ASCT) followed by a high dose of therapy was introduced. -Osserman, E.F.; DiRe, L.B.; DiRe, J.; Sherman, W.H.; Hersman, J.A.; Storb, R. Identical twin marrow transplantation in multiple myeloma. Acta Haematol. 1982, 68, 215223.
  • 4. FDA APPROVALS OF PIS -Past, Present, and a Glance into the Future of Multiple Myeloma Treatment Weam Othman Elbezanti et al 2023
  • 5. MECHANISM OF ACTION OF PIS Past, Present, and a Glance into the Future of Multiple Myeloma Treatment. Weam Othman Elbezanti et.al, March 23.
  • 6. CURRENT STANDARD OF CARE FOR NDMM RVD TRIPLET, SWOG S0777 TRIAL
  • 7. RVD APPROVAL FRONTLINE- SWOG S0777 TRIAL
  • 10. CARFILZOMIB IN RELAPSED MYELOMA- ASPIRE TRIAL
  • 19. 33% of patients had Unfavourable Cytogenetics 45% sCR rate after 4 cycles. 24 months PFS- 92%.
  • 20. JASEILEC ET AL , 2020
  • 27. 60 months PFS- 72% and OS- 84% High risk cytogenetics- 57% and 72% respectively MRD negativity -60% after 8 cycles Grade III and IV cardiac events 3%
  • 28. ROUSELL ET. AL. 2021 ASH
  • 33. Median PFS -56months and median OS not reached High rates of MRD negativity even after induction
  • 35. 474 NDMM pts were randomized (KRd_ASCT, n=158; KRd12, n=157; KCd_ASCT, n=159).
  • 37. KRD ASCT > KRD > KCD ASCT
  • 38. RVD Vs KRD Head to head- Endurance trial 2020
  • 43. No significant difference between KRD and RVD without HSCT. Trial excluded High risk Patients
  • 44. LIST OF STUDIES DOCUMENTING MRD Current Main Topics in Multiple Myeloma
  • 45. FOR CARFILZOMIB Deeper and quicker responses- high rate of sCR rates post induction High rate of MRD negativity in trials Activity against High risk myeloma Cardiac toxicity , though of caution, is seen in low number of patients. Deeper responses can be cost effective in long run.