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Meeting in a Box

17th Annual International Congress on Hematologic Malignancies ® : Focus on Leukemias , Lymphomas, and Myeloma. Meeting in a Box. Multiple myeloma . What Can We Learn From Multiple Myeloma Genomic Analysis?. Nikhil Munshi , MD. Genomic Analysis Takeaways.

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Meeting in a Box

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  1. 17th Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas, and Myeloma Meeting in a Box

  2. Multiple myeloma

  3. What Can We Learn From Multiple Myeloma Genomic Analysis? Nikhil Munshi, MD

  4. Genomic Analysis Takeaways • Methods of genomic analysis • Established techniques: cytogenetics, FISH • Emerging techniques: RNA- and DNA-based arrays, transcript-processing arrays, genomic sequencing, and proteomics • Current goals of genomic analysis in myeloma • Understand the biology of myeloma • Identify risk categories to improve prognostication • Identify and validate novel targets • Develop biologic agents that target the myeloma cell • Ultimately, develop personalized therapy • Currently, gene expression profiling has prognostic value, predicting survival of patients with different genomic signatures, but it cannot yet predict response to therapy.

  5. High-Risk Smoldering Myeloma – Should We Intervene Early? Ola Landgren, MD, PhD

  6. Smoldering Myeloma • Definition of smoldering myeloma1 • Serum monoclonal IgG or IgA ≥ 3 g/dL and/or clonal bone marrow plasma cells ≥ 10% AND • Absence of end-organ damage (ie, hypercalcemia, renal insufficiency, anemia, or bone lesions attributed to plasma cell proliferative disorder) • Overall risk of progression2 • 10% per year in years 0-5 • 3% per year in years 6-10 • 1% per year in years 11-20 • Risk stratification • Mayo Clinic analysis3 stratifies patients according to their 5-yr risk of progression into 3 groups: 25% risk, 51% risk, and 76% risk • PETHEMA Study Group analysis4 stratifies patients according to their 5-yr risk of progression into 3 groups: 4% risk, 46% risk, and 72% risk • e 1Kyle RA, et al. Leukemia. 2010;24:1121-7. 2Kyle RA, et al. N Engl J Med. 2007;356:2582-90. 3Dispenzieri A, et al. Blood. 2008;111:785-9. 4Perez-Persona E, et al. Blood. 2007;110:2586-92.

  7. First Randomized Phase III Trial for Smoldering Myeloma Randomization of high-risksmoldering MM patients: Median time to symptomatic progression Len/dex: not yet reached Observation: 21 months 4-year overall survival Len/dex: 94% Observation: 85% Lenalidomide 25 mg/day, D1-21 Dexamethasone 20 mg D1-D4 and D12-D15 Therapeutic abstention Induction:Nine 28-day cycles Lenalidomide 10 mg/day, D1-21 every 2 months Therapeutic abstention Maintenance:Until progression Primary endpoint: time to progression to symptomatic MM Secondary endpoints: ORR, DOR, PFS, OS, and safety and tolerability HR = 5.67; P < .0001 HR = 3.5; P < .01 Mateos MV, et al. ASH 2011. Abstract 991.

  8. Smoldering Myeloma Takeaways • Current clinical recommendation for smoldering myeloma: no treatment unless part of a clinical trial1 • Better understanding of pathogenesis from MGUS to myeloma needed: • To develop better biological markers • To predict a patient’s risk of progression • To develop early intervention strategies 1Kyle R, et al. Int’l Myeloma Working Group. Leukemia 2010.

  9. Current Trends: Treatment Strategies for Newly Diagnosed Elderly Patients With Myeloma James Berenson, MD

  10. Dexamethasone ± LenalidomideSWOG S0232 Dexamethasone (n = 95) Placebo: 25 mg/day, D1-28 Dex: 40 mg/day, D1-4, 9-12, 17-20 Three 35-day cycles Len + Dex (n = 97) Len: 25 mg/day, D1-28 Dex: 40 mg/day, D1-4, 9-12, 17-20 Three 35-day cycles Disease progression Responding/stable disease Len + Dex Len: 25 mg/day, D1-21 Dex: 40 mg/day, D1-4 and 15-18 28-day cycles until progression Dexamethasone Placebo: 25 mg/day, D1-21 Dex: 40 mg/day, D1-21 28-day cycles until progression Unblinded Treatment Len: 25 mg/day, D1-28 Dex: 40 mg/day, D1-4, 9-12, 17-20 Three 35-day cycles Unblinded Len + Dex Len: 25 mg/day, D1-21 Dex: 40 mg/day, D1-4 and 15-18 Objective: to determine the efficacy and safety of Len + Dex as induction therapy in NDMM patients Primary endpoint: PFS Zonder JA, et al. Blood. 2010;116:5838-41.

  11. Dexamethasone ± LenalidomideSWOG S0232 • 1-yr PFS was significantly improved with the addition of lenalidomide (78% vs 53%; P = .002) ORR = 78% ORR, P < .0001 VGPR, P < .001 ORR = 48% Zonder JA, et al. Blood. 2010;116:5838-41.

  12. Lenalidomide + High-Dose Dexvs Lenalidomide + Low-Dose Dex: ECOG E4A03 Lenalidomide + High-Dose Dexamethasone (RD)a Len: 25 mg/day, days 1-21 Dex: 40 mg/day, days 1-4, 9-12, 17-20 (n = 223) Transplant-eligible patients can proceed to SCT Four 28-day cycles Lenalidomide + Low-Dose Dexamethasone (Rd) Len: 25 mg/day, days 1-21 Dex: 40 mg/day, days 1, 8, 15, 22 (n = 222) Continue therapy until disease progression Objective: to assess if a reduced dose of dex decreases toxicity while maintaining efficacy Primary endpoint: ORR after first 4 cycles aBasedon the superiority of the Rd regimen, the study was stopped at a median follow-up of 12.5 months and patients in the RD arm crossed over to Rd therapy. Survival significantly improved with Rd (low-dose) regimen (P = .0002 at 1 year) Rajkumar SV, et al. Lancet Oncol. 2010;11:29-37.

  13. Study Schema: R A N D O M I Z E ARM A (VMP) VMP: Four 6-week cycles: Cycles 1-4 Bortezomib 1.3mg/m2 days 1, 4, 8, 11, 22, 25, 29, 32; Melphalan 9mg/m2 and prednisone 60mg/m2 days 1-4 Followed by five 6-week cycles: Cycles 5-9 Bortezomib 1.3mg/m2 days 1, 8, 22, 29; Melphalan9mg/m2 and prednisone 60mg/m2 once daily on days 1–4 Max of 9 cycles (total 54 weeks) in both arms ARM B (MP) MP: Nine 6-week cycles: Cycles 1-9 Melphalan 9mg/m2 and prednisone 60mg/m2 days 1-4 MP ± Bortezomib: VISTA • Endpoints: Primary: TTP; Secondary: CR, ORR, TTR, DOR, PFS, TNT, OS, QoL Previously untreated patients; not candidates for transplant • 3-yr OS: 72% in VMP arm vs 69.5% in MP arm • 682 patients randomized • 151 centers • 22 countries worldwide • IDMC recommended study stop in September 2007 based on protocol-specified interim analysis • VMP was significantly superior for all efficacy endpoints San Miguel J, et al. N Engl J Med. 2008;359:906-17. Mateos MV, et al. J ClinOncol. 2010;28:2259-66.

  14. Phase II Studies for Newly Diagnosed Multiple Myeloma 1Reeder CB, et al. ASCO 2008. Abstract 8517. 2Berenson JR, et al. Br J Haematol. 2011;155:580-7. 3Richardson PG, et al. Blood. 2009;114:501-2. 4Berenson JR, et al. Eur J Haematol. 2009;82:433-9. 5Niesvizky R, et al. Blood. 2008;111:1101-9. 6Rossi A, et al. ASCO 2011. Abstract 8008. 7Jakubowiak AJ, et al. Blood. 2012;120:1801-9. 8Mikhael J, et al. ASCO 2012. Abstract 8010. 9Kolb B, et al. ASCO 2012. Abstract 8009.

  15. Novel Combinations and New Drugs for Elderly Patients With Myeloma • Approved drugs • Novel combinations • Modifications of dose and schedule • Improve efficacy • Better tolerability • Drugs in development • Similar targets • Proteasome inhibitors - carfilzomib(FDA-approved!), ixazomib • IMiDs - pomalidomide (FDA-approved!) • New classes of agents • Monoclonal antibodies - anti-CS-1 (elotuzumab), anti-CD40 (dacetuzumab), anti-CD38 • mTOR inhibitors - temsirolimus • PI3K inhibitors - perifosine • HDAC inhibitors - vorinostat, romidepsin, panobinostat

  16. Maintenance Therapy – Is It for Everyone? Nikhil Munshi, MD

  17. Maintenance Therapy for Multiple Myeloma • Maintenance therapy: • Purpose is to prolong remission duration and life expectancy • Requires periodic follow-up to monitor toxicity and response • Patient must have: • Disease that is in remission (undetectable or at a low level) • Recovered from all previous toxicities • Maintenance agent must have: • Minimal toxicity or at least not overlapping with the toxicity of the induction regimen • Convenient dosing • Convenient route of administration

  18. Lenalidomide Maintenance After Transplant: CALGB 100104 Restaging Days 90–100 Registration Randomization • D-S Stage 1-3, < 70 years • > 2 cycles of induction • Attained SD or better •  1 yr from start of therapy • > 2 x 106 CD34 cells/kg • Mel 200 • ASCT Placebo • CR • PR • SD Lenalidomide 10 mg/d with ↑↓ (5–15 mg) McCarthy PL, et al. N Engl J Med. 2012;366:1770-81.

  19. Lenalidomide Maintenance Following Lenalidomide Consolidation: IFM 2005-02 Phase III randomized, placebo-controlled trial N= 614 patients, from 78 centers, enrolled between 7/2006 and 8/2008 • PFS significantly prolonged with lenalidomide maintenance compared with placebo (41 vs 24 months; P < 10-9) • OS not significantly different between groups (P = .79) Patients age < 65 years, with nonprogressivedisease, ≤ 6 months after ASCT in first line Randomization: stratified according to Beta-2m, del13, VGPR Consolidation: Lenalidomide alone 25 mg/day po days 1-21 of every 28 days for 2 months Arm A = Placebo (N=307) until relapse Arm B = Lenalidomide (N=307) 10-15 mg/d until relapse Primary endpoint: PFS Secondary endpoints: CR rate, TTP, OS, feasibility of long-term lenalidomide… Attal M, et al. Proc International Myeloma Workshop 2011. McCarthy P, et al. Proc International Myeloma Workshop 2011.

  20. Lenalidomide Maintenance in Patients Ineligible for Transplant: MM-015 Open- Label Double- Blind Treatment Phase Extension Phase Cycles (28 day) 1-9 Cycles 10+ MPR-R Maintenance M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 Lenalidomide 10 mg/day R: 10 mg/day po , days 1-21 days 1 - 21 MPR RANDOMIZATION Lenalidomide M: 0.18 mg/kg, days 1-4 Disease (25 mg/day) P: 2 mg/kg, days 1-4 Placebo Progression +/- Dexamethasone R: 10 mg/day po , days 1-21 MP M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 Placebo PBO: days 1 -21 • PFS significantly prolonged with the addition of lenalidomide maintenance following MPR induction therapy (HR = 0.349; P < .001) • PFS benefit maintained across patient subgroups Palumbo A, et al. N Engl J Med. 2012;366:1759-69.

  21. Maintenance Lenalidomide and Second Primary Malignancies • Both CALGB 100104 and IFM 2005-002 showed increased risk of second primary malignancies compared with placebo (23 vs6 and 18 vs4, respectively)1,2 • MM-015 also showed increase in frequency of second primary malignancies with lenalidomide use (n=12, MPR-R; n=10, MPR; n=4, MP) 1Attal M, et al. Proc International Myeloma Workshop 2011. 2McCarthy P, et al. Proc International Myeloma Workshop 2011. 3Palumbo A, et al. N Engl J Med. 2012;366:1759-69.

  22. PAD + Bortezomib Maintenance vs VAD + Thalidomide Maintenance: HOVON Trial MM Stage II or III, Age 18–65 Randomization 3 x PAD 3 x VAD CAD + GCSF CAD + GCSF MEL 200 + PBSCT MEL 200 + PBSCT In GMMG 2nd MEL 200 + PBSCT Allogeneic Tx In GMMG 2nd MEL 200 + PBSCT Bortezomib maintenance 1.3 mg/m2/2 weeks for 2 yrs Thalidomide maintenance 50 mg/day for 2 yrs Sonneveld P, et al. ASH 2010. Abstract 40.

  23. Bortezomib + Thalidomide vs Bortezomib + Prednisone as Maintenance: GEM2005MAS65 Series of 260 elderlyuntreated MM patientsincluded in the GEM2005 Spanishtrial Bort/Mel/Pred (VMP) Bort/Thal/Pred (VTP) Induction (6 cycles) vs No significantdifferencesbetweenVMP and VTP in ORR (80% and 81%) and CR rate (20% and 27%) Bort/Pred (VP) Bort/Thal (VT) Bort/Pred (VP) Bort/Thal (VT) Maintenance Mateos MV, et al. Lancet Oncol. 2010;10:934-41.

  24. Conclusions About Maintenance Therapy for Multiple Myeloma • Maintenance therapy prolongs PFS. • Low-dose oral agents preferable for maintenance therapy. • Both bortezomib and lenalidomide are useful maintenance agents and may need to be combined for patients with high-risk disease. • Slight increase in incidence of secondary malignancy after lenalidomide maintenance. • Overall, everyone who meets prerequisites for maintenance therapy should be considered candidates for treatment.

  25. How to Best Use New Proteasome Inhibitors and IMiDs in Myeloma SundarJagannath, MD

  26. Pivotal Trial of Immunomodulatory Agent Pomalidomide: MM-002 Progressive disease • Primary endpoint: PFS • Secondary endpoints: ORR, DOR, OS, and safety Randomization Progressive disease Progressive disease Option to add LoDEXa(40 mg/week) Discontinue and follow-up for survival and subsequent treatment POM (4 mg days 1–21 of 28-day cycles) POM (4 mg days 1–21 of 28-day cycles) + LoDEXa(40 mg/week) Aspirin (80–100 mg) or equivalent mandated for all patients. aPatients aged > 75 yrs had starting DEX dose of 20 mg/week.

  27. MM-002: Response Rates • Median number of cycles received = 5 (range, 1-28) • Disease control rate = 81% overall Jagannath S, et al. ASH 2012. Abstract 450.

  28. MM-002: PFS, OS, and Safety • Other AEs of clinical relevance in POM +/- LoDEX: • Febrile neutropenia: 3% • Peripheral neuropathy (grade1/2): 13% (none > grade 2) • DVT: 2% Jagannath S, et al. ASH 2012. Abstract 450.

  29. Pomalidomide + Low-Dose DEX vsHigh-Dose DEX: MM-003 Stratification • Age (≤ 75 vs > 75 yrs) • Number of prior Tx ( 2 vs > 2) • Disease population 28-day cycles (n = 302) POM: 4 mg/day D1-21 + LoDEX: 40 mg (≤ 75 yrs) 20 mg (> 75 yrs) D1, 8, 15, 22 RANDOMIZATION 2:1 PD* orintolerable AE Follow-up for OS and SPM until 5 years post enrollment (n = 153) HiDEX: 40 mg (≤ 75 yrs) 20 mg (> 75 yrs) D1-4, 9-12, 17-20 Companion trialMM-003C POM 21/28 days PD* Thromboprophylaxisindicated for those receiving POM or with DVT history *Progression of disease independently adjudicated in real-time

  30. MM-003: PFS and OS Dimopoulos MA, et al. ASH 2012. Abstract LBA-6.

  31. Pivotal Trial of Proteasome Inhibitor Carfilzomib: 003-A1 003-A0 003-A1 MM: Progressive disease > 2 prior therapy lines including bortezomib, thalidomide or lenalidomide, an alkylating agent, and anthracycline alone or in combination Carfilzomib 20 mg/m2 days 1, 2, 8, 9, 15, 16 every 28 days N = 46 Carfilzomib Dose escalation to 27 mg/m2 after cycle 1 up to 12 cycles N = 266 Primary Endpoint: ORR Secondary Endpoints: clinical benefit rate (≥ minimal response), DOR, PFS, OS, and safety

  32. Single-Agent Carfilzomib Pivotal Trial: Efficacy Siegel DS, et al. Blood. 2012;120:2817-25.

  33. Single-Agent Carfilzomib Pivotal Trial: Safety • Other AEs (any grade) of clinical relevance: • Dyspnea in 34%; 17% due to carfilzomib • CHF in 3.8%; myocardial infarction or cardiac arrest in 2.3% Siegel DS, et al. Blood. 2012;120:2817-25.

  34. Multiple Myeloma Takeaways • Genomic analysis is an important area of research that is expanding rapidly, but to date it has had limited use in the myeloma clinic, restricted to its ability to predict survival on the basis of gene expression profiling. • Active monitoring remains optimal approach for smoldering myeloma, although this may change in the future with further examination of lenalidomide/dexamethasone treatment. • Elderly patients with newly diagnosed multiple myeloma can be treated with a number of distinct regimens, depending on their comorbidities and performance status. These include lenalidomide/low-dose dexamethasone and VMP (bortezomib, melphalan, and prednisone). • Maintenance therapy with a convenient, low-toxicity regimen is suggested for all myeloma patients meeting the following criteria: achievement of remission and no ongoing toxicity. • Proteasome inhibitor carfilzomib and IMiDpomalidomide recently granted accelerated approval by FDA for treatment of relapsed/refractory myeloma, on the basis of promising response rates, and PFS and OS results in this heavily pretreated population.

  35. Lymphoma

  36. Initial Management of Peripheral T-Cell Lymphoma: If CHOP Is No Good, What Is? Steven M. Horwitz, MD

  37. Peripheral T-Cell Lymphoma Summary • With PTCL, first-line CHOP produces ORR of 60-80+%, CR of 30-60+%, and durable remissions <20-30%. For most patients, CHOP is inadequate. • Adding therapy to a CHOP backbone is feasible but: (1) benefit not equivalent in all subtypes,1 and (2) toxicity soon outweighs benefit because regimen operating near MTD.2,3 • ASCT has shown promise in some upfront trials with PTCL.4,5 • Potential approaches to explore: • CHOP + etoposide • CHOP + novel agent (ie, brentuximab data very encouraging) • CHOP → maintenance therapy • ASCT • Entirely new regimen • Current standard of care should be clinical trial, whenever possible. 1Kim SJ. Eur J Cancer. 2012;48:3223-31. 2Kim JG, et al. Cancer Chemother Pharmacol. 2007;60:129-34. 3Gallamini A, et al. Blood. 2007;110:2316-23. 4Reimer P, et al. J Clin Oncol. 2009;27:106-13. 5d’Amore F, et al. J Clin Oncol. 2012;30:3093-9.

  38. Management of Cutaneous T-Cell Lymphoma Lauren Pinter-Brown, MD, FACP

  39. Treatment and Supportive Care of Cutaneous T-Cell Lymphoma • Treatment of mycosis fungoides and Sezary’s syndrome generally involves skin-directed therapy for early-stage (IA-IIA) and systemic therapy for later stages (≥IIB) or when skin-directed therapy fails. • Skin-directed therapies: topical agents (corticosteroids, imiquimod, chemotherapy, retinoids), phototherapy, radiation therapy • Systemic therapies: extracorporeal photochemotherapy, retinoids, interferon-alpha or gamma, alemtuzumab, denileukindiftitox (not currently available), HDAC inhibitors, chemotherapy • Treatment considerations: stage, route (oral vs topical vs systemic), rapidity of response, availability (geographically or due to cost), and comorbidities • Supportive care: • Pruritus: distinguish generalized from localized; treat with moisturizers, emollients, and barrier protection, as well as topical steroids, camphor/menthol, others • Infection: crucial to avoid central lines and maintain skin barrier. Consider bleach baths.

  40. Treatment of CD30+ Lymphoproliferative Disorders • Lymphomatoidpapulosis: • Treatment options: watch and wait (most cases), methotrexate, phototherapy, interferon • Rapid relapse off treatment, so maintenance therapy necessary • 10%-20% of these cases associated with Hodgkin lymphoma, mycosis fungoides, or ALCL, so follow-up required • Primary cutaneous ALCL: • Treatment options: skin-directed therapy, surgical resection, XRT, chemotherapy only with extracutaneous involvement (CHOP not recommended), retinoids, interferon, thalidomide, steroids, excimer laser. • 90% 5-year overall survival • Spontaneous remission possible

  41. How I Manage Early-Stage Diffuse Large B-Cell Lymphoma Daniel O. Persky, MD

  42. Current Treatment Paradigm for Early-Stage DLBCL • Early-stage DLBCL is curable malignancy, with >50% cure rate and a 70%-90% 5-year OS.1 • Differences in outcomes arise from variations in radiation therapy quality and patient selection • Early-stage disease has pattern of late relapses • Addition of rituximab to chemotherapy modestly improved PFS outcomes in early-stage disease, but has not improved OS.2,3 • Another option for early-stage DLBCL is R-CHOP x 3-4 (short course) → IFRT, which showed favorable results in a retrospective comparison to standard R-CHOP.4 1Miller TP. J Clin Oncol. 2004;22:2982-4. 2Ketterer N, et al. Ann Oncol. 2013;24:1032-7. 3Pfreundschuh M, et al. Lancet Oncol. 2011;12:1013-22. 4Terada Y, et al. ASH 2012. Abstract 1628.

  43. Novel Approaches for Early-Stage DLBCL • Radioimmunotherapy consolidation: • SWOG 0313:1CHOP x 3 + IFRT →ibritumomab: 4-yr est. PFS = 84% • E3402:2 R-CHOP → ibritumomab→ IFRT (if PET+): 4-yr PFS = 88%, OS = 98% • PET risk-adapted therapy – mid-treatment PET prognostically significant in DLBCL3,4 • BCCA experience:5 R-CHOP x 3→ PET. If PET+, go on to IFRT. If PET‒, receive R-CHOP x 1 • Ongoing phase II trial, S1001, will test this PET risk-adapted approach in early-stage DLBCL, with PET+ population receiving R-CHOP x 3 → IFRT → ibritumomab 1Miller TP, et al. ASH 2008. Abstract 3598. 2Witzig T, et al. ASH 2012. Abstract 2687. 3Haioun C, et al. Blood. 2005;106:1376-81. 4Spaepen K, et al. Ann Oncol. 2002;13:1356-63. 5Sehn et al, Lugano 2008. Abstract 052; Sehn LH, et al. Lugano 2011. Abstract 028.

  44. Biology of Early-Stage DLBCL • DLBCL molecularly heterogeneous with different 5-year survivals:1 • Primary mediastinal: 64% • Germinal center B-cell-like (GCB): 59% • Activated B-cell-like (ABC): 30% • GCB appears more prevalent in early-stage disease2 and with superior survival3 after R-CHOP compared with ABC • Bottom line: Biology of early-stage DLBCL needs further exploration. 1Rosenwald A, et al. J Exp Med. 2003;198:851-62. 2Lenz G, et al. N Engl J Med. 2008;359:2313-23. 3Lenz G, et al. N Engl J Med. 2010;362:1417-29.

  45. Advanced-Stage DLBCL Craig Moskowitz, MD

  46. R-CHOP Regimens for Advanced-Stage DLBCL • R-CHOP21 vs R-CHOP14 phase III studies • GELA:1 3-yr EFS similar (60% vs 56%; HR = 1.04; P = .76) • UK:2 2-yr OS similar (81% vs 83%; HR = 0.95; P = .70) • Current strategy: R-CHOP21 x 6-8 cycles → 2nd-line treatment if < CR3 • MSKCC:4 R-CHOP → ibritumomab • For those receiving RIT, 2-yr PFS = 79%, 2-yr OS = 84% • Led to current US phase III trial: • R-CHOP→ ibritumomabconsolidation in elderly DLBCL 1Delarue R, et al. Lancet Oncol. 2013;14:525-33. 2Cunningham D, et al. ASCO 2011. Abstract 8000. 3NCCN NHL guidelines. 2013. 4Hamlin PA, et al. ASH 2010. Abstract 1793.

  47. Risk-Adapted Therapy for Advanced-Stage DLBCL • MSKCC 01-142: • MSKCC 08-026: • Results showed no difference in PFS among:1 • PET-negative • PET-positive/biopsy-negative • PET-positive/biopsy-positive R-C1000HOuncappedP-14 x 4 + - PET Repeat Bx Bx - Bx + ICE x 2 RICE x 1 HDT/ASCT ICE x 3 followed by observation • Results showed 4-yr OS > 80% and 4-yr PFS > 70% R-R-C1000HOuncappedP-14 x 3 C1000HOuncappedP-21 x 1 + - PET Repeat Bx Bx - Bx + ≥80% Ki-67 <80% Augmented RICE x 2 followed by HDT/ASCT ICE x 3 followed by observation Augmented RICE x 2 followed by observation 1Moskowitz et al. Lancet Oncol. 2010;28:1896-903.

  48. Dose-Adjusted EPOCH-R for Advanced-Stage DLBCL • CALGB phase II study1 • Excellent 5-yr results in overall population • OS = 84% • PFS = 81% • EFS = 75% • However, high-risk disease associated with worse outcomes than other subgroups • IPI high-risk group, OS = 43% • ABC OS inferior to GCB (P = .04) • Ki67 < 60% OS inferior to ≥ 60% (P = .05) • Ongoing phase III CALGB 50303: dose-adjusted EPOCH-R vs R-CHOP21 1Wilson WH, et al. Haematologica. 2012;97:758-65.

  49. Relapsed DLBCL in the Rituximab Era AnasYounes, MD

  50. Salvage Phase III Trials in Relapsed DLBCL:R-ICE + BEAM/ASCT Remains Standard • CORAL:1 Randomized patients who relapsed after CHOP ±R to R-ICE or R-DHAP. Those achieving CR or PR then received BEAM ASCT. • No difference between salvage therapies in OS (P = .49) or PFS (P = .44). • Among those who relapsed within 12 months after diagnosis, prior rituximab associated with poor EFS (P = .001). • Among those who relapsed more than 12 months after diagnosis, prior rituximab status had no impact on EFS (P = .11). • Bio-CORAL:2 subset of patients from CORAL trial with histologic material available. Tumors classified as GCB or ABC. • Among those receiving R-ICE, histologic type did not impact PFS (P = .82) or OS (P = .96). • Among those receiving R-DHAP, patients with GCB tumors had significantly better PFS (P = .005) and potentially better OS (P = .06) compared with patients with ABC tumors. 1Gisselbrecht, et al. J ClinOncol. 2010;28:4184-90. 2Thieblemont et al. J ClinOncol. 2011;29:4079-87.

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