Approaches for Relapsed & Refractory Multiple Myeloma Robert Z. - - PowerPoint PPT Presentation

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Approaches for Relapsed & Refractory Multiple Myeloma Robert Z. - - PowerPoint PPT Presentation

Feb 29, 2024 252 likes •571 views

Approaches for Relapsed & Refractory Multiple Myeloma Robert Z. Orlowski, M.D., Ph.D. Florence Maude Thomas Cancer Research Professor Chair, ad interim , Department of Lymphoma/Myeloma Chair, SWOG Myeloma Committee Principal Investigator,

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Approaches for Relapsed & Refractory Multiple Myeloma

Robert Z. Orlowski, M.D., Ph.D.

Florence Maude Thomas Cancer Research Professor Chair, ad interim, Department of Lymphoma/Myeloma Chair, SWOG Myeloma Committee Principal Investigator, LLS SCOR in High-risk Plasma Cell Dyscrasias Twitter handle: @Myeloma_Doc

Zinc Co de : E M/ I XZ/ 1218/ 0032 Da te o f Pre pa ra tio n: No ve mb e r 2018

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Definition of Relapsed/Refractory

  • Progression on therapy in patients who achieve minor response

(MR) or better, or who progress within 60 days of their last therapy.

  • Patients who never achieve at least an MR to initial induction

therapy and progress while on therapy are defined as “primary refractory.”

Rajkumar, SV et al. Blood 117: 4691, 2011.

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Options for Relapsed/Refractory Disease

NCCN Guidelines V 2.2019; www.nccn.org

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APEX (1-3 Priors) : Bortezomib vs. Dex

Richardson, PG et al. N Engl J Med. 352:2487, 2005.

78% improvement in median time-to-progression

Time (days)

P = .0001

Proportion of patients

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 450

Median TTP Bortezomib Dexamethasone Bortezomib Dexamethasone All Pts Post-1st relapse 6.2 mos 3.5 mos 7.0 mos 5.6 mos

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DOXIL-MMY-3001 : (≥1 Priors)

Orlowski, RZ et al. J Clin Oncol. 25:3892, 2007.

PLD + Bortezomib 9.3 months Bortezomib 6.5 months

Statistical analysis: HR (95% CI) 1.82 (1.41-2.35) p = 0.000004

Percent of Patients Progression-Free 100 200 300 400 500 20 40 60 80 100

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Len/Dex vs. Dex (≥1 Priors)

Weber, DM et al. N. Engl. J. Med. 357:2133, 2007.

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PANORAMA (≥2 Priors) : PFS

  • Clinically relevant increase in PFS of 3.9 months

San Miguel, JF et al. Lancet Oncol. 15:1195, 2014.

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Carfilzomib (≥2 Priors)

Siegel, DS et al. Blood 120:2817, 2012.

  • Results from PX-171-

003-A1 study of carfilzomib in patients with relapsed and refractory myeloma

  • ORR of 23.7%

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ASPIRE (1-3 Priors) : Response Rates

Stewart, AK et al. N Engl J Med. 372:142, 2015.

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Pomalidomide (≥2 Priors)

Richardson, PG et al. Blood 123:1826, 2014.

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ENDEAVOR (1-3 Priors) : PFS by ITT

Dimopoulos, MA et al. Lancet Oncol. 17:27, 2016.

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TOURMALINE1 (≥1 Priors) : Key Data

Moreau, P et al. N Engl J Med. 374:1621, 2016.

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Safety Profile

Moreau, P et al. N Engl J Med. 374:1621, 2016.

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Impact on High-risk Patients

Avet-Loiseau, H et al. Blood 130: 2610, 2017.

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SIRIUS (≥3 Priors) : Response Data

Lonial, S et al. Lancet 387:1551, 2016.

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Daratumumab + Bortez/Dex (≥1 Priors)

Palumbo, A et al. N Engl J Med. 375:754, 2016.

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Daratumumab + Len/Dex (≥1 Priors)

Dimopoulos, MA et al. N Engl J Med. 375 :1319, 2016.

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ELOQUENT2 (1-3 Priors) : PFS Curves

Lonial, S et al. N Engl J Med. 373:621, 2015.

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Daratumumab/ Pomalidomide/ Dexamethasone (≥2 Priors)

Chari, A et al. Blood 130:974, 2017.

  • ORR was 58%

in double refractory patients

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ARROW Trial (2 or 3 Priors)

Mateos, MV et al. 2018 ASCO Abstract # 8000.

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PFS Data

Mateos, MV et al. 2018 ASCO Abstract # 8000.

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Selected AEs

Mateos, MV et al. 2018 ASCO Abstract # 8000.

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OPTIMISMM Trial (1-3 Priors)

Richardson, P et al. 2018 ASCO Abstract # 8001.

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PFS Data

Richardson, P et al. 2018 ASCO Abstract # 8001.

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Selected AEs

Richardson, P et al. 2018 ASCO Abstract # 8001.

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Elotuzumab/Pomalidomide/dex

Richardson, P et al. 2018 ASCO Abstract # 8001.

10.3 months 4.7 months

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Other Approaches

  • CAR T-cells

– bb2121, LCAR-B38M

  • Novel small molecules

– Selinexor, venetoclax

  • Novel immunotherapies

– Isatuximab, GSK2857916, BiTEs

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Options Overview : Relapsed

Kunacheewa C & Orlowski RZ. Annu Rev Med., 2019, in press.

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Options : Bortez & Len Refractory

Kunacheewa C & Orlowski RZ. Annu Rev Med., 2019, in press.

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Options : Dual Refractory

Kunacheewa C & Orlowski RZ. Annu Rev Med., 2019, in press.

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