Multiple Myeloma Update from the American Society of Clinical . Ppt Powerpoint Presentation slides-Medical Slideshow ASH/FDA Workshop on Clinical Endpoints in Multiple Myeloma

Multiple Myeloma Update from the American Society of Clinical .

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Slide 1 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Welcome and Introduction Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring: Moderator: Richard Lutes, MD

Slide 2 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Upfront Therapy Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring:

Slide 3 :

Lenalidomide/high-dose dexamethasone vs lenalidomide/low-dose dexamethasone (ECOG trial E4A03) Rajkumar SV, et al, ASCO 2007, Abstract LBA8025. 25 20 15 10 5 0 0 0.2 0.6 1 Overall survival (mo) Probability 0.8 0.4 Log-rank P=0.0001 Rd RD A B

Slide 4 :

Rajkumar SV, et al, ASCO 2007, Abstract LBA8025. Lenalidomide/high-dose dexamethasone vs lenalidomide/low-dose dexamethasone (ECOG trial E4A03)

Slide 5 :

Rajkumar SV, et al, ASCO 2007, Abstract LBA8025. Lenalidomide/high-dose dexamethasone vs lenalidomide/low-dose dexamethasone (ECOG trial E4A03)

Slide 6 :

Melphalan-prednisone-thalidomide (MPT) vs melphalan-prednisone (MP) in patients aged =75 years (IFM 01-01 trial) hulin c, et al, ASCO 2007, Abstract 8001.

Slide :

Slide 8 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Upfront Therapy Discussion Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring: Moderator: Richard Lutes, MD

Slide 9 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Transplantation Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring:

Slide 10 :

TTIII plus bortezomib Barlogie B, et al, ASCO 2007, Abstract 8020. 0 20 60 100 Months from Start of Induction 80 40 PR nCR CR Percent of patients (%)

Slide 11 :

TTIII plus bortezomib Barlogie B, et al, ASCO 2007, Abstract 8020.

Slide 12 :

Alternating bortezomib and dexamethasone as induction regimen in younger MM patients Rosinol L, et al, ASCO 2007, Abstract 8024. End of Induction Treatment (n=40) Best Response Ever Achieved (n=40) ORR: 77.5% ORR: 82.5%

Slide 13 :

Alternating bortezomib and dexamethasone as induction regimen in younger MM patients Rosinol L, et al, ASCO 2007, Abstract 8024. Liver Gastrointestinal Peripheral Neuropathy Thrombocytopenia Percent Neutropenia Skin Grade 1 Grade 2 Grade 3 0 100 80 Fatigue

Slide 14 :

Characteristics of patients relapsing after autologous stem cell transplant Mahmood ST, et al, ASCO 2007, Abstract 8022.

Slide 15 :

Mel-based autotransplants for MM Retrospective analysis of 2836 transplant patients identified 5 factors that could influence outcomes Type of treatment (tandem transplant or not) Presence of cytogenetic abnormality High ß2-microglobulin Low albumin Low platelet counts Pineda-Roman M, et al, ASCO 2007, Abstract 8043.

Slide 16 :

Reduced intensity conditioning 32 patients with relapsed/refractory MM 19 patients with HLA-identical sibling donor 5 patients had disease progression 4 patients in complete remission 5 patients in PR or VGPR 13 patients with no HLA-identical donor 11 patients had disease progression Overall, 6 patients died from treatment-related mortality (incidence, 33%) Mohty M, et al, ASCO 2007, Abstract 8045.

Slide 17 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Transplantation Discussion Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring: Moderator: Richard Lutes, MD

Slide 18 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Treating Relapsed/Refractory Disease Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring:

Slide 19 :

Pegylated doxorubicin (PLD) and bortezomib vs bortezomib alone *According to IMWG 2006 criteria. Harousseau JL, et al, ASCO 2007, Abstract 8002.

Slide 20 :

Pegylated doxorubicin (PLD) and bortezomib vs bortezomib alone Harousseau JL, et al, ASCO 2007, Abstract 8002. 0 20 60 100 Time (d) Percent of Subjects Alive (%) 80 40 PLD + Bortezomib Bortezomib Overall survival Median follow-up time: 14 mo

Slide 21 :

Effect of prior thalidomide treatment on efficacy of pegylated doxorubicin (PLD) and bortezomib *Treatment by subgroup (IMiD exposed, IMiD naïve) interaction test from the Cox model. Sonneveld P, et al, ASCO 2007, Abstract 8023.

Slide 22 :

Effect of prior thalidomide treatment on efficacy of pegylated doxorubicin (PLD) and bortezomib *According to IMWG criteria. Sonneveld P, et al, ASCO 2007, Abstract 8023.

Slide 23 :

Factors predictive of outcome in patients treated with bortezomib, melphalan, prednisone, and thalidomide (VMPT) Palumbo AP, et al, ASCO 2007, Abstract 8048. Months P=0.02 = PR < PR Age: 65 years Response: PR rate Proportion of Patients Months P=0.19 <65 years =65 years Proportion of Patients

Slide 24 :

Factors predictive of outcome in patients treated with bortezomib, melphalan, prednisone, and thalidomide (VMPT) Palumbo AP, et al, ASCO 2007, Abstract 8048. Months P=0.98 Del (13) No Deletion ?2-microglobulin Deletion (13) Proportion of Patients Months P=0.06 ?2m <3.5 mg/dL ?2m >3.5 mg/dL Proportion of Patients

Slide 25 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Novel Agents Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring:

Slide 26 :

Tanespimycin + bortezomib in relapsed/refractory MM Tanespimycin (17-AAG/KOS 953) disrupts heat shock protein 90 (hsp90), a molecular chaperone that transports proteins critical for MM growth, survival, and drug resistance Phase I dose escalation study in 49 patients 7th dose level reached so far Combination treatment was well tolerated Combination treatment resulted in inhibition of hsp90 and proteasome activity Richardson PG, et al, ASCO 2007, Abstract 3532.

Slide 27 :

Phase I evaluation of carfilzomib (PR-171) in hematologic malignancies Carfilzomib is a novel irreversible proteasome inhibitor Promotes >80% proteasome inhibition in the blood Dose-limiting toxicities Myelosuppression: cyclic reversible thrombocytopenia and neutropenia A “first dose effect” has occurred at doses =20 mg/m2 and heralds rapid decline in M-protein Objective responses have been observed at doses of carfilzomib ranging from 11 mg/m2 to 27 mg/m2 Rapid onset of response (<1 month) Responses are durable (4 to >9.5 months) Responses noted in bortezomib and IMiD failures Stable disease for >1 year Stewart KA, et al, ASCO 2007, Abstract 8003.

Slide 28 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Novel Agents Discussion Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring: Moderator: Richard Lutes, MD

Slide 29 :

Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting Final Thoughts Nikhil Munshi, MD Dana-Farber Cancer Institute Boston, MA S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN Featuring: Moderator: Richard Lutes, MD

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Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting. more Multiple Myeloma Update from the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting. Treating Relapsed/Refractory Disease. Nikhil Munshi, MD ... less

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