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Hematology Highlights ASCO 2011

Hematology Highlights ASCO 2011. Don M Benson Jr MD PhD The Ohio State University Comprehensive Cancer Center. Overview. Acute leukemia Chronic lymphocytic leukemia Lymphoma Myeloma.

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Hematology Highlights ASCO 2011

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  1. Hematology HighlightsASCO 2011 Don M Benson Jr MD PhD The Ohio State University Comprehensive Cancer Center

  2. Overview • Acute leukemia • Chronic lymphocytic leukemia • Lymphoma • Myeloma

  3. #6504 : Results from a randomized phase III trial of decitabine versus supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed AML • Largest trial to date of this kind: • Decitabine 20mg/m2 IV • Given daily for 5 days q 4 weeks • Best supportive care (physician discretion) or, • Low-dose cytarabine 20mg/m2 SQ • Given daily for 10 days q 4 weeks • Age 65 and older

  4. #6504 : Results from a randomized phase III trial of decitabine versus supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed AML Treatment Arm n Duration of Rx median OS CR+CRp Decitabine 242 4.4 7.7 (6.2-9.2) 18% BSC / cytarabine 243 2.4 5.0 (4.3-6.3) 8% OS was not different (p=.10) at the time of planned interim analysis. OS was different after updated follow up, however, nominal p = 0.03 in favor of the decitabine arm. AEs were similar in both arms – Grade 3 and 4 hematologic toxicities and febrile neutropenia were most common

  5. n=53 pts (med age 74) with newly diagnosed AML Decitabine 20mg/m2 IV days 1-10 64% CR/CRi rate after median 3 cycles PFS median 46 weeks OS median 55 weeks

  6. Comparison of 10 day decitabine vs 5 day decitabine in AML 10 day regimen 5 day regimen

  7. Chronic lymphocytic leukemia • Abstract 6623: daniciclib, a novel CDK inhibitor • Abstract 6508: a novel BTK inhibitor

  8. #6623 : Phase I study of the CDK inhibitor dinaciclib (SCH727965) in patients with relapsed/refractory CLL • Dinaciclib is a potent inhibitor of CDK 1, 2, 5, and 9 • Preclinical data shows promising activity in CLL • Same class of drug as Flavopiridol, more potent in preclinical models • Phase I dose escalation study: • 5mg/m2 • 7mg/m2 • 10mg/m2 • 14mg/m2 • 17mg/m2 • n=33 patients enrolled

  9. #6623 : Phase I study of the CDK inhibitor dinaciclib (SCH727965) in patients with relapsed/refractory CLL Post cycle 7: 8.8 x 5.4 cm Pre treatment: 17 x 9.2 cm

  10. #6623 : Phase I study of the CDK inhibitor dinaciclib (SCH727965) in patients with relapsed/refractory CLL Median prior lines = 4 62% bulky disease 38% 17p deletion SAEs: - sepsis related fatality (level 2) - TLS in n = 5 patients Response rate = 45% 14mg/m2 selected as phase II dose Median PFS not reached

  11. #6508 : Activity and tolerability of the Bruton’s tyrosine kinase (BTK) inhibitor PCI-32765 in patients with CLL/SLL: interim results of a phase Ib/II study • BCR signaling is abnormally activated in CLL • BTK is essential to BCR signaling and is overexpressed in CLL1 • PCI-32765 leads to apoptosis in preclinical models • Two cohorts enrolled (n=78 pts to date, n=39 evaluable) • Previously untreated • At least 2 prior therapies, including fludarabine • 87% of patients enrolled at least 1 high risk feature (e.g., 17p del, IgVHunmutated status) • PCI-32765 administered po daily at 420mg and 840mg 1Blood 2011; e-pub ahead of print Mar 11

  12. #6508 : Activity and tolerability of the Bruton’s tyrosine kinase (BTK) inhibitor PCI-32765 in patients with CLL/SLL: interim results of a phase Ib/II study • Median follow up 4 months: • 44% PR • 5% CR • 89% nodal response rate • n = 4 of 12 pts with 17p del have responding, 7 others remain on study with improving SD • At present, n=34 of 39 pts in the 420mg cohort remain on study with only 1 PD documented

  13. Lymphoma • Abstract 8001: SWOG S9704 • Abstract 8004: CORAL final results • Abstract 8031: SGN-35

  14. #8801 : Randomized phase III trial (SWOG S9704) of R/CHOP x 8 vs. R/CHOP x 6 with autoSCT for aggressive diffuse large B cell lymphoma • Is there a role for autoSCT in first remission? • R/CHOP x 5 then randomize: • R/CHOP x 1 and autoSCT • R/CHOP x 3 • n=397 patients • Age < 65, Bulky stage II – IV disease, 35% had high IPI • Primary endpoints PFS and OS at 2 years

  15. #8801 : Randomized phase III trial (SWOG S9704) of R/CHOP x 8 vs. R/CHOP x 6 with autoSCT for aggressive diffuse large B cell lymphoma • n = 253 of 370 randomized* • R/CHOP x 8 n=128 • autoSCT n=125 Overall Results: PFS (%) p-value R/CHOP x 8 56 0.005 autoSCT 69 - no difference in OS (71% for R/CHOP and 74% for autoSCT) * n=66 progressed and n=23 refused randomization

  16. #8801 : Randomized phase III trial (SWOG S9704) of R/CHOP x 8 vs. R/CHOP x 6 with autoSCT for aggressive diffuse large B cell lymphoma • Exploratory analysis for patients with high IPI: Outcome: R/CHOP autoSCTp-value PFS 41 75 0.02 OS 64 82 0.01 .

  17. #8801 : Randomized phase III trial (SWOG S9704) of R/CHOP x 8 vs. R/CHOP x 6 with autoSCT for aggressive diffuse large B cell lymphoma • Conclusions: • Early autoSCT improves PFS for responding patients with advanced stage DLBCL • May be particularly important therapeutic approach for patients with high IPI score

  18. #8804 : Maintenance with rituximab after autologous SCT in relapsed patients with CD20(+) DLBCL: CORAL final analysis • 477 pts with relapsed DLBCL enrolled1 • Salvage: • R/ICE n=243 • R/DHAP n=234 • No differences in response rate, EFS or OS at 4 years based on salvage regimen utilized. 1 J ClinOncol2010;28:4184-90

  19. #8804 : Maintenance with rituximab after autologous SCT in relapsed patients with CD20(+) DLBCL: CORAL final analysis • Following autoSCT: • Rituximab maintenance n= 122 • Observation n=120 • No differences overall in long-term EFS or OS as a function of rituximab maintenance post-autoSCT

  20. #8031: Results from a pivotal phase II study of brentuximabvedotin (SGN-35) in pts with relapsed or refractory Hodgkin lymphoma • Brentuximabvedotin (SGN-35) is an anti-CD30 mAb conjugated to monomethylauristatin E (MMAE) • Selectively induces apoptosis in CD30(+) cells • Trial to evaluate objective response rate in patients with relapsed/refractory HL post autoSCT • 102 patients enrolled • Median age 31, median 3.5 prior therapies before autoSCT • 71% primary refractory, 42% did not respond to previous therapy

  21. #8031: Results from a pivotal phase II study of brentuximabvedotin (SGN-35) in pts with relapsed or refractory Hodgkin lymphoma • Overall response rate = 75% • Complete response 34% • Median duration of response not yet reached • Range 0.3 – 61.4 weeks • Median follow up = 9 months for responding patients • SAE included neutropenia, sensory neuropathy, thrombocytopenia and anemia • Single agent SGN-35 shows activity in r/r HL. • In this heavily pre-treated population, 34% achieved CR and 65% of these patients remain in CR at time of presentation

  22. Myeloma • Abstract 8067: Pomalidomide • Abstract 8027: Carfilzomib • Abstract 8076: Elotuzumab

  23. #8031: Efficacy of pomalidomide + low dose dexamethasone in multiple myeloma pts previously treated with lenalidomide • Pomalidomide is a novel IMID agent • 1-3 prior lines of therapy, including lenalidomide • Pomalidomide 4mg with dex 40mg days 1, 8, 15, 22 • 61 pts enrolled: • 47% prior bortezomib, 77% prior auto transplant • ORR 48% • 12% VGPR, 23% PR, 13% MR (and 42% SD)

  24. #8027: PX-171-003-A1, phase II study of carfilzomib in pts with relapsed/refractory MM: long-term follow up • Carfilzomib is a novel proteosome inhibitor • n=266 pts enrolled with 3 or more prior therapies • Had to include IMID, bortezomib, and alkylator • 36% of pts responded with median duration of 7 months, median OS 15.5 months • Depth of response did not correlate with duration of response

  25. #8076: Phase I trial of elotuzumab + lenalidomide and low-dose dex in pts with relapsed/refractory MM • Elotuzumab is an anti-CS1 monoclonal antibody • n=29 pts, med prior therapies = 3 • PR or better in 82% • 95% in lenalidomide-naïve • 83% in patients refractory to last line of therapy • Median PFS not reached at 12.7 months follow up

  26. Summary • AML • 5-day decitabine inferior to 10-day regimen • CLL • Novel CDK inhibitor and BTK inhibitor show promise • Lymphoma • autoSCT in first remission for DLBCL, especially high IPI • Maintenance rituximab after autoSCT of no benefit in DLBCL • SGN-35 shows promising activity in relapsed/refractory HL • Myeloma • Pomalidomide, Carfilzomib, Elotuzumab on the horizon

  27. Other notable abstracts • Abstract 8034: advanced stage HL patients with negative PET post-chemotherapy are at low risk of relapse and may not require additional XRT • Abstract 8032: SGN-35 shows 86% RR in anaplastic large cell lymphoma • Abstract 6500: COMFORT-I trial shows activity of INCB18424, an oral JAK1/2 inhibitor in patients with MF • Abstract 6503: CLASSIC 1 trial shows clofarabine and cytarabine improves ORR and EFS in older patients with relapsed/refractory AML

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