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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.
Thank You!!!
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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.