Update on Treatment for Lymphoma Lymphoma Support Ireland Meeting 19-02-2011 Dr. Greg Korpanty Medical Oncology Registrar ...
What is Lymphoma ? <ul><li>Lymphoma is a malignant transformation of  lymphocytes (white blood cells) </li></ul><ul><li>Ly...
 
 
 
 
CLP, common lymphoid precursor; BLB, pre-B lymphoblast; DN, CD4/CD8 double-negative pro-T cell; DP, CD4/CD8 double-positiv...
 
Classification of Lymphoma <ul><li>Histopathological </li></ul><ul><ul><li>NHL vs HL </li></ul></ul><ul><ul><li>B vs T-cel...
 
Histopathological classification Lymphoma Non-Hodgkin Lymphoma 85% Hodgkin Lymphoma 15% B-cell NHL 80% T-cell NHL 20%
 
New cases:  65,540 Deaths:  20,210
Etiology <ul><li>The exact etiology is unknown </li></ul><ul><li>Immune suppression </li></ul><ul><ul><li>congenital (Wisk...
Etiology <ul><li>Chronic inflammation </li></ul><ul><ul><li>Helicobacter pylori  (gastric NHL) </li></ul></ul><ul><ul><li>...
Diagnosis <ul><li>History </li></ul><ul><ul><li>fatigue </li></ul></ul><ul><ul><li>weight loss </li></ul></ul><ul><ul><li>...
Diagnosis <ul><li>Blood tests </li></ul><ul><li>- FBC, R/L  </li></ul><ul><li>-  LDH ,  uric acid </li></ul><ul><li>Bone m...
 
 
Treatment <ul><li>Multidisciplinary approach: </li></ul><ul><li>- pathology </li></ul><ul><li>- medical oncology </li></ul...
Follicular (indolent) lymphoma
Follicular lymphoma (FL) <ul><li>10-15% in Stage I or II </li></ul><ul><ul><li>potentially curable </li></ul></ul><ul><ul>...
Management of FL <ul><li>Observation – watch & wait </li></ul><ul><li>Local radiotherapy </li></ul><ul><li>Systemic chemot...
Rituximab
Rituximab
Bexxar, Zevalin
When we treat FL <ul><li>Symptoms </li></ul><ul><li>- fatigue </li></ul><ul><li>- pain </li></ul><ul><li>Organ dysfunction...
Bendamustine + Rituximab vs R-CHOP  in Indolent NHL  <ul><li>Regimen: bendamustine 90 mg/m 2  on Days 1 and 2 + Rituximab ...
Bendamustine + Rituximab vs R-CHOP in Indolent NHL: AEs  Rummel M, et al. ASH 2009. Abstract 405. Parameter Bendamustine +...
GELA PRIMA Phase III Study: Rituximab Maintenance in FL CHOP  x 6 + Rituximab  x 8 CVP  x 8 + Rituximab  x 8 FCM  x 6 + Ri...
Rituximab Maintenance for 2 Yrs:  PRIMA Phase III Study Salles GA, et al. ASCO 2010. Abstract 8004. At 2 yrs, rituximab ar...
 
Preliminary Analysis of Rituximab vs Watch and Wait in Asymptomatic FL Pts Ardeshna K, et al. ASH 2010. Abstract 6. Progre...
Bendamustine in Rituximab-Refractory NHL (Phase III Single-Arm Study) <ul><li>Pivotal evaluation of bendamustine for treat...
<ul><li>ORR  </li></ul><ul><ul><li>Patients with ≥ 1 dose of bendamustine (n = 100):  75% </li></ul></ul><ul><ul><li>Patie...
Rituximab ± Bortezomib in Relapsed, Rituximab-Naive or -Sensitive FL Coiffier B, et al. ASH 2010. Abstract 857. Rituximab ...
Results Coiffier B, et al. ASH 2010. Abstract 857. Response, n (%) Bort + Ritux (n = 315) Ritux  (n = 324) P Value ORR 199...
Grade ≥ 3 Toxicities <ul><li>Peripheral neuropathy </li></ul><ul><ul><li>Overall: 16% vs 1% in bortezomib + rituximab and ...
Post-Treatment FDG PET-CT as Predictor of PFS in FL: PRIMA Analysis <ul><li>PRIMA database reviewed  to identify PET-CT sc...
Diffuse Large B-Cell Lymphoma (DLBCL)
Management of DLBCL <ul><li>Systemic chemotherapy </li></ul><ul><li>Stem cell or bone marrow transplant </li></ul><ul><li>...
CHOP(R) Chemotherapy C yclophosphamide (Cytoxan) H ydroxydaunorubicin (Adriamycin) O ncovin (vincristine) P rednisone R it...
LNH 03-2B: R-ACVBP vs R-CHOP in Treatment-Naive Pts With CD20+ DLBCL <ul><li>Patients aged 18-59 yrs </li></ul><ul><li>No ...
LNH 03-2B Study: Results  Récher C, et al. ASH 2010. Abstract 109. 3-Yr PFS 1.0 Survival Probability 0.8 0.6 0.4 0.2 0 0 1...
T-Cell Lymphoma
 
 
Romidepsin in Progressive or Relapsed PTCL: Phase II Data <ul><li>Novel, bicyclic histone deacetylase inhibitor approved f...
Hodgkin’s Lymphoma
1798 - 1866 Thomas Hodgkin
HL <ul><li>One-seventh as common as NHL </li></ul><ul><li>Highly treatable and curable, even when disseminated </li></ul><...
Management of HL <ul><li>Radiotherapy </li></ul><ul><li>Systemic chemotherapy </li></ul><ul><li>Stem cell/bone marrow tran...
<ul><li>A driamycin (doxorubicin) </li></ul><ul><li>B leomycin </li></ul><ul><li>V inblastine </li></ul><ul><li>D acarbazi...
E2496: ABVD vs Stanford V ± Radiation Therapy in Advanced Hodgkin Lymphoma Gordon LI, et al. ASH 2010. Abstract 415. ABVD ...
E2496: Results <ul><li>ABVD remains standard of care  </li></ul><ul><li>5-yr FFS: higher for ABVD </li></ul><ul><li>Simila...
Brentuximab Vedotin (SGN-35) in Relapsed/ Refractory Hodgkin’s Lymphoma  <ul><li>Brentuximab vedotin anti-CD30 monoclonal ...
 
Brentuximab Vedotin (SGN-35) in Relapsed/Refractory HL: Results  <ul><li>94%  of patients achieved tumor reduction </li></...
Novel Therapies Under Investigation in Lymphomas
CAL-101 <ul><li>CAL-101: isoform-selective inhibitor of PI3K [1] </li></ul><ul><ul><li>Dosed at 50 mg BID up to 350 mg BID...
KW-0761 <ul><li>KW-0761: anti-CCXR4 monoclonal antibody </li></ul><ul><ul><li>Given at 1.0 mg/kg for 8 weekly infusions to...
Conclusions <ul><li>1. Selected group of DLBCL patients may benefit from more aggressive treatment than standard R-CHOP ch...
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Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011 - pc

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Presentation by Dr Greg Korpanty, Beaumont Hospital, Dublin on Update on Lymphoma Treatment to meeting Feb 19th 2011.

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  • Lymphoma is a very broad term.
  • Findings from a recent trial conducted by Rummel and colleagues evaluating bendamustine and rituximab vs R-CHOP as first-line therapy for patients with advanced FL, MCL, and indolent NHL showed significantly higher complete response and progression-free survival among patients on bendamustine plus rituximab vs those on R-CHOP ( P = .0323 and P =.0002, respectively). Progression-free survival among patients with follicular lymphoma was significantly higher among patients receiving bendamustine plus rituximab therapy vs those on R-CHOP ( P = .02).
  • Higher rates of grade 3/4 neutropenia and leukocytopenia were reported in the R-CHOP group, as well as use of G-CSF and alopecia ( P &lt; .0001 for all comparisons). More patients receiving R-CHOP developed infections and peripheral neuropathy compared with those on bendamustine plus rituximab ( P = .0403 and P &lt; .0001, respectively).
  • In the phase III GELA PRIMA study, patients who achieved complete or partial response after initial therapy were randomly assigned to receive maintenance rituximab or observation for 2 years. The primary endpoint of this study was progression-free survival, and study endpoints were event-free survival and overall survival.
  • Recently reported findings showed that patients on maintenance rituximab elicited a significantly higher 2-year PFS rate vs observation ( P &lt; .0001) and also had response rates and improved time to next anti-lymphoma treatment. However, maintenance rituximab also was associated with higher rates of grade 3/4 neutropenia and infections.
  • CI, confidence interval; FL, follicular lymphoma; HR, hazard ratio; M, maintenance; PFS, progression-free survival; R4, rituximab; RM, rituximab maintenance; W + W, watch and wait.
  • Bendamustine was evaluated in a single-arm, phase III trial among patients with rituximab-refractory NHL. Bendamustine 120 mg/m 2 was given on Days 1 and 2 every 21 days for 6-8 cycles as long as response to stable disease was maintained. Primary endpoints of the study included overall response rates and duration of response, and secondary endpoints were progression-free survival and safety.
  • Results showed overall response rates were 75% among patients who received at least one dose of bendamustine (n = 100), 88% among those who had at least a partial response to the previous treatment regimen (n = 51), and 64% among those who did not respond to the last regimen (n = 36). There were no significant differences in response rates by histology. Median PFS was reported to be 9.3 months, and median duration of response was 9.2 months.
  • FL, follicular lymphoma; FLIPI, Follicular Lymphoma International Prognostic Index.
  • Bort, bortezomib; CI, confidence interval; CR, complete response; HR, hazard ratio; IRC, Independent Review Committee; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; Ritux, rituximab; SD, stable disease.
  • PN, peripheral neuropathy.
  • CI, confidence interval; FDG; fluorodeoxyglucose; HR, hazard ratio; NR, not reported; PET-CT, positron emission tomography–computed tomography; PFS, progression-free survival.
  • CNS, central nervous system; CR/CRu, complete response/unconfirmed complete response; FDS, disease-free survival; DLBCL, diffuse large B-cell lymphoma; EFS, event-free survival; IFM, ifosfamide; IT-MTX, intrathecal methotrexate; MTX, methotrexate; OS, overall survival; PFS, progression-free survival; R-ACVBP rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone; R-CHOP; rituximab plus cyclophosphamide, doxorubicin, prednisone, vincristine.
  • FES, event-free survival; HR, hazard ratio; PFS, progression-free survival; R-ACVBP rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone; R-CHOP; rituximab plus cyclophosphamide, doxorubicin, prednisone, vincristine. .
  • CR, complete response; Cru, unconfirmed complete response; IRC, independent review committee; PD, progressive disease; PR, partial response; PTCL, peripheral T-cell lymphoma; SD, stable disease.
  • ABVD, bleomycin, dacarbazine, doxorubicin, vinblastine; HL, Hodgkin lymphoma; IFRT, involved-field radiation therapy; PA, posteroanterior.
  • ABVD, bleomycin, dacarbazine, doxorubicin, vinblastine; CCR, complete response + clinical complete response; CR, complete response; FFS, failure-free survival; OS, overall survival; PD, progressive disease; PR partial response; SD, stable disease.
  • ASCT, autologous stem cell transplantation; CR, complete response; ECOG, Eastern Cooperative Oncology Group; CR, complete response; OS, overall survival; PFS, progression-free survival; PR, partial response; PS, performance score; SD, stable disease.
  • CR, complete response; HL, Hodgkin lymphoma; Inv., investigator; IRF, independent review facility; ORR, overall response rate; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease.
  • BID, twice daily; NHL, non-Hodgkin’s lymphoma.
  • CR, complete response; ORR, overall response rate; PR, partial response.
  • Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011 - pc

    1. 1. Update on Treatment for Lymphoma Lymphoma Support Ireland Meeting 19-02-2011 Dr. Greg Korpanty Medical Oncology Registrar Beaumont Hospital
    2. 2. What is Lymphoma ? <ul><li>Lymphoma is a malignant transformation of lymphocytes (white blood cells) </li></ul><ul><li>Lymphocytes (B-cell and T-cell) </li></ul><ul><ul><li>involved in immune response to infection, transplanted organs or foreign bodies </li></ul></ul><ul><ul><li>They are carried through lymphatic system as well as the blood, so lymphoma can start both in lymph nodes and spread anywhere throughout the body </li></ul></ul><ul><ul><li>Lymphoma can also start in ANY solid organ of the body </li></ul></ul><ul><ul><li>- GI tract </li></ul></ul><ul><ul><li>- skin </li></ul></ul><ul><ul><li>- lung </li></ul></ul><ul><ul><li>- heart </li></ul></ul><ul><ul><li>- CNS </li></ul></ul><ul><ul><li>- bones </li></ul></ul>
    3. 7. CLP, common lymphoid precursor; BLB, pre-B lymphoblast; DN, CD4/CD8 double-negative pro-T cell; DP, CD4/CD8 double-positive pre-T cell; GC, germinal-center B cell; MC, mantle B cell; MZ, marginal zone B cell; NBC, naive B cell; PTC, peripheral T cell.
    4. 9. Classification of Lymphoma <ul><li>Histopathological </li></ul><ul><ul><li>NHL vs HL </li></ul></ul><ul><ul><li>B vs T-cell </li></ul></ul><ul><ul><li>CD20 +ve vs CD20 -ve </li></ul></ul><ul><ul><li>high grade vs low grade </li></ul></ul><ul><li>Clinical </li></ul><ul><ul><li>aggressive vs indolent </li></ul></ul><ul><ul><li>stage I vs IV </li></ul></ul><ul><li>Molecular </li></ul><ul><ul><li>c-myc gene translocation </li></ul></ul>
    5. 11. Histopathological classification Lymphoma Non-Hodgkin Lymphoma 85% Hodgkin Lymphoma 15% B-cell NHL 80% T-cell NHL 20%
    6. 13. New cases: 65,540 Deaths: 20,210
    7. 14. Etiology <ul><li>The exact etiology is unknown </li></ul><ul><li>Immune suppression </li></ul><ul><ul><li>congenital (Wiskott-Aldrich syndrome) </li></ul></ul><ul><ul><li>organ transplant (immunosupressants) </li></ul></ul><ul><ul><li>HIV infection </li></ul></ul><ul><ul><li>increasing age </li></ul></ul><ul><li>DNA repair defects </li></ul><ul><ul><li>ataxia telangiectasia </li></ul></ul><ul><ul><li>xeroderma pigmentosum </li></ul></ul>
    8. 15. Etiology <ul><li>Chronic inflammation </li></ul><ul><ul><li>Helicobacter pylori (gastric NHL) </li></ul></ul><ul><ul><li>Chlamydia psittaci (ocular, adnexal NHL) </li></ul></ul><ul><li>Viral causes </li></ul><ul><ul><li>EBV - Burkitt’s lymphoma </li></ul></ul><ul><ul><li>HTLV-I - T cell leukemia-lymphoma </li></ul></ul><ul><ul><li>HTLV-V - cutaneous T cell lymphoma </li></ul></ul><ul><ul><li>Hepatitis C </li></ul></ul>
    9. 16. Diagnosis <ul><li>History </li></ul><ul><ul><li>fatigue </li></ul></ul><ul><ul><li>weight loss </li></ul></ul><ul><ul><li>fevers </li></ul></ul><ul><ul><li>night sweats </li></ul></ul><ul><ul><li>lump </li></ul></ul><ul><li>Physical examination </li></ul><ul><ul><li>lump(s) </li></ul></ul><ul><ul><li>enlarged liver, spleen </li></ul></ul><ul><ul><li>pale skin; bruises </li></ul></ul>
    10. 17. Diagnosis <ul><li>Blood tests </li></ul><ul><li>- FBC, R/L </li></ul><ul><li>- LDH , uric acid </li></ul><ul><li>Bone marrow biopsy </li></ul><ul><li>Imaging </li></ul><ul><li>- CXR </li></ul><ul><li>- CT N/T/A/P </li></ul><ul><li>- PET/CT scan </li></ul>
    11. 20. Treatment <ul><li>Multidisciplinary approach: </li></ul><ul><li>- pathology </li></ul><ul><li>- medical oncology </li></ul><ul><li>- haematology </li></ul><ul><li>- radiation oncology </li></ul><ul><li>- radiology </li></ul><ul><li>Chemotherapy </li></ul><ul><li>- combination CT </li></ul><ul><li>- high dose CT + Bone marrow Tx </li></ul><ul><li>Radiotherapy </li></ul>
    12. 21. Follicular (indolent) lymphoma
    13. 22. Follicular lymphoma (FL) <ul><li>10-15% in Stage I or II </li></ul><ul><ul><li>potentially curable </li></ul></ul><ul><ul><li>local radiotherapy </li></ul></ul><ul><li>85-90% Stage III or IV </li></ul><ul><ul><li>incurable but treatable </li></ul></ul><ul><ul><li>treatment provides symptoms control </li></ul></ul>
    14. 23. Management of FL <ul><li>Observation – watch & wait </li></ul><ul><li>Local radiotherapy </li></ul><ul><li>Systemic chemotherapy </li></ul><ul><ul><li>IV agents: CHOP, CVP, fludarabine, cladribine. </li></ul></ul><ul><ul><li>oral agents: chlorambucil and prednisone </li></ul></ul><ul><li>Monoclonal antibody against CD20 </li></ul><ul><ul><li>Rituximab </li></ul></ul><ul><ul><li>Bexxar, Zevalin </li></ul></ul><ul><li>(Stem cell or bone marrow transplant) ? </li></ul>
    15. 24. Rituximab
    16. 25. Rituximab
    17. 26. Bexxar, Zevalin
    18. 27. When we treat FL <ul><li>Symptoms </li></ul><ul><li>- fatigue </li></ul><ul><li>- pain </li></ul><ul><li>Organ dysfunction </li></ul><ul><li>Cosmetic considerations </li></ul><ul><li>Low Hgb, Plts, WBC </li></ul>
    19. 28. Bendamustine + Rituximab vs R-CHOP in Indolent NHL <ul><li>Regimen: bendamustine 90 mg/m 2 on Days 1 and 2 + Rituximab on Day 1 every 28 days </li></ul>Rummel M, et al. ASH 2009. Abstract 405. Parameter Bendamustine + Rituximab R-CHOP P Value CR, % 39.6 30.0 .0262 Median PFS, mos 54.9 34.8 .00012
    20. 29. Bendamustine + Rituximab vs R-CHOP in Indolent NHL: AEs Rummel M, et al. ASH 2009. Abstract 405. Parameter Bendamustine + Rituximab R-CHOP P Value Grade 3/4 neutropenia, 10.7 46.5 < .0001 Grade 3/4 leukocytopenia, 12.1 38.2 < .0001 G-CSF use 4 20 < .0001 Infections, n 96 127 .0025 Erythema, n 42 23 .0122 Allergic skin reaction, n 40 15 .0003 Paresthesias, n 18 73 < .0001 Stomatitis 16 47 < .0001
    21. 30. GELA PRIMA Phase III Study: Rituximab Maintenance in FL CHOP x 6 + Rituximab x 8 CVP x 8 + Rituximab x 8 FCM x 6 + Rituximab x 8 Patients with previously untreated grade 1-3 FL (N = 1200) CR, PR RANDOMI ZED Maintenance Rituximab 375 mg/m 2 q2mo x 2 yrs Observation Available at: http://prima.gela.org.
    22. 31. Rituximab Maintenance for 2 Yrs: PRIMA Phase III Study Salles GA, et al. ASCO 2010. Abstract 8004. At 2 yrs, rituximab arm had significant improvements in time to next antilymphoma treatment and RR PFS 95% CI P Value Rituximab, % 82 (2 yrs) 78-86 < .0001 Observation, % 66 (2 yrs) 61-70 Grade 3/4 Adverse Events Rituximab Overall: 23% Neutropenia: 4% Infections: 4% Observation Overall: 16% Neutropenia: < 1% Infections: < 1%
    23. 33. Preliminary Analysis of Rituximab vs Watch and Wait in Asymptomatic FL Pts Ardeshna K, et al. ASH 2010. Abstract 6. Progression-free survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 1 2 3 4 5 Proportion of Patients Progression Free Yrs From Randomization 3-Yr PFS W + W: 33% R4: 60% R4 + RM: 81% W + W R4 R4 + RM Events 108 33 33 Pts 181 83 189
    24. 34. Bendamustine in Rituximab-Refractory NHL (Phase III Single-Arm Study) <ul><li>Pivotal evaluation of bendamustine for treatment of rituximab-refractory, indolent, B-cell NHL </li></ul><ul><li>Bendamustine 120 mg/m 2 given on Days 1 and 2 every 21 days </li></ul>Kahl BS, et al. Cancer. 2010;116:106-114.
    25. 35. <ul><li>ORR </li></ul><ul><ul><li>Patients with ≥ 1 dose of bendamustine (n = 100): 75% </li></ul></ul><ul><ul><li>Patients with ≥ PR to last regimen (n = 51): 88% </li></ul></ul><ul><ul><li>Patients with no response to last regimen (n = 36): 64% </li></ul></ul><ul><li>Response rates did not significantly differ by </li></ul><ul><li>histology </li></ul><ul><li>Median PFS: 9.3 mos </li></ul>Bendamustine in Rituximab-Refractory NHL: Phase III Results Kahl BS, et al. Cancer. 2010;116:106-114.
    26. 36. Rituximab ± Bortezomib in Relapsed, Rituximab-Naive or -Sensitive FL Coiffier B, et al. ASH 2010. Abstract 857. Rituximab 375 mg/m 2 Cycle 1: Days 1, 8, 15, 22 Cycles 2-5: Day 1 only Rituximab + Bortezomib Rituximab 375 mg/m 2 Cycle 1: Days 1, 8, 15, 22 Cycles 2-5: Day 1 only + Bortezomib 1.6 mg/m 2 Cycle 1: Days 1, 8, 15, 22 25 Wks Patients with relapsed, rituximab-naive or -sensitive FL (N = 670)
    27. 37. Results Coiffier B, et al. ASH 2010. Abstract 857. Response, n (%) Bort + Ritux (n = 315) Ritux (n = 324) P Value ORR 199 (63) 160 (49) < .001 CR 79 (25) 59 (18) .035 SD 78 (25) 120 (37) -- PD 38 (12) 44 (14) -- Overall durable response rate 159 (50) 124 (38) .002 Durable CR 76 (24) 54 (17) -- 100 90 80 70 60 50 40 30 20 10 0 48 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Patients Without Event (%) Mos Median PFS (95% CI) 11.0 mos (9.1-12.0) 12.8 mos (11.5-15.0) Rituximab: Bortezomib-rituximab : HR: 0.822 (0.681-0.991; P = .039)
    28. 38. Grade ≥ 3 Toxicities <ul><li>Peripheral neuropathy </li></ul><ul><ul><li>Overall: 16% vs 1% in bortezomib + rituximab and rituximab pts, respectively </li></ul></ul><ul><ul><li>Most PN events were reversible in bortezomib pts </li></ul></ul>Coiffier B, et al. ASH 2010. Abstract 857. Adverse Event, n (%) Bortezomib + Rituximab (n = 334) Rituximab (n = 339) Constipation 1 (< 1) 0 Diarrhea 25 (7) 0 Fatigue 5 (1) 0 Nausea/Vomiting 10 (3) 2 (1) Neutropenia 37 (11) 15 (4) Febrile neutropenia 5 (1) 3 (1) Infections 36 (11) 15 (4) Herpes zoster 12 (4) 1 (< 1) Peripheral sensory neuropathy 9 (3) 0 Thrombocytopenia 10 (3) 2 (1)
    29. 39. Post-Treatment FDG PET-CT as Predictor of PFS in FL: PRIMA Analysis <ul><li>PRIMA database reviewed to identify PET-CT scans at staging and assessment for response post induction </li></ul><ul><li>277 scans (160 patients of total PRIMA population [N = 1217]) </li></ul><ul><li>Posttreatment PET shown to an independent predictor and stronger than other prognostic factors </li></ul>Trotman J, et al. ASH 2010. Abstract 855. Mos 60 0 6 12 18 24 30 36 42 48 54 1.0 0.8 0.6 0.4 0.2 0 Probability of PFS 74% 32% PET negative PET positive HR = 3.5 (95% CI: 2.0-6.1) P < .0001
    30. 40. Diffuse Large B-Cell Lymphoma (DLBCL)
    31. 41. Management of DLBCL <ul><li>Systemic chemotherapy </li></ul><ul><li>Stem cell or bone marrow transplant </li></ul><ul><li>Radiotherapy (palliative) </li></ul>
    32. 42. CHOP(R) Chemotherapy C yclophosphamide (Cytoxan) H ydroxydaunorubicin (Adriamycin) O ncovin (vincristine) P rednisone R ituximab
    33. 43. LNH 03-2B: R-ACVBP vs R-CHOP in Treatment-Naive Pts With CD20+ DLBCL <ul><li>Patients aged 18-59 yrs </li></ul><ul><li>No radiotherapy in either treatment arm </li></ul>Récher C, et al. ASH 2010. Abstract 109.
    34. 44. LNH 03-2B Study: Results Récher C, et al. ASH 2010. Abstract 109. 3-Yr PFS 1.0 Survival Probability 0.8 0.6 0.4 0.2 0 0 12 24 36 48 60 72 Mos P = .0015; HR: 0.482 R-ACVBP R-CHOP 3-Yr OS 1.0 Survival Probability 0.8 0.6 0.4 0.2 0 0 12 24 36 48 60 72 Mos P = .0071; HR: 0.439 R-ACVBP R-CHOP
    35. 45. T-Cell Lymphoma
    36. 48. Romidepsin in Progressive or Relapsed PTCL: Phase II Data <ul><li>Novel, bicyclic histone deacetylase inhibitor approved for cutaneous </li></ul><ul><li>T-cell lymphoma </li></ul><ul><li>Current trial: single-arm, international, open-label phase II study (N = 131) </li></ul><ul><li>Romidepsin given at 14 mg/m 2 (4-hr IV) on Days 1, 8, and 15 of a 28-day cycle for 6 cycles </li></ul>Coiffier B, et al. ASH 2010. Abstract 114. Response, n (%) IRC (N = 130) Investigators (N = 130) Objective response 34 (26) 38 (29) Complete response 17 (13) 21 (16) SD 32 (25) 22 (17) PD 64 (49) 70 (54)
    37. 49. Hodgkin’s Lymphoma
    38. 50. 1798 - 1866 Thomas Hodgkin
    39. 51. HL <ul><li>One-seventh as common as NHL </li></ul><ul><li>Highly treatable and curable, even when disseminated </li></ul><ul><li>Presence of Reed-Sternberg cell is mandatory for diagnosis. </li></ul>
    40. 52. Management of HL <ul><li>Radiotherapy </li></ul><ul><li>Systemic chemotherapy </li></ul><ul><li>Stem cell/bone marrow transplant </li></ul>
    41. 53. <ul><li>A driamycin (doxorubicin) </li></ul><ul><li>B leomycin </li></ul><ul><li>V inblastine </li></ul><ul><li>D acarbazine </li></ul>
    42. 54. E2496: ABVD vs Stanford V ± Radiation Therapy in Advanced Hodgkin Lymphoma Gordon LI, et al. ASH 2010. Abstract 415. ABVD 6-8 cycles modified IFRT 36 Gy only in patients with massive mediastinal disease (n = 404) Stanford V - MOPPEBVCAD 12 wks’ chemotherapy, modified IFRT 36 Gy to sites > 5 cm in max transverse dimension (n = 408) *Defined as mass ≥ 1/3 maximum intrathoracic diameter on standing PA chest x-ray. Previously untreated patients with histologically proven HL, advanced or locally extensive disease, massive mediastinal adenopathy* (N = 812)
    43. 55. E2496: Results <ul><li>ABVD remains standard of care </li></ul><ul><li>5-yr FFS: higher for ABVD </li></ul><ul><li>Similar rates of toxicity between treatment arms </li></ul><ul><ul><li>Higher rates of grade 3 lymphopenia sensory neuropathy with Stanford V </li></ul></ul>Gordon LI, et al. ASH 2010. Abstract 415. Measure, % ABVD Stanford V Response* CR + CCR 72.0 69.0 PR 7.7 7.4 SD 7.9 10.3 PD < 1.0 2.0 5-yr FFS* 73.0 71.0 5-yr OS* 88.0 87.0
    44. 56. Brentuximab Vedotin (SGN-35) in Relapsed/ Refractory Hodgkin’s Lymphoma <ul><li>Brentuximab vedotin anti-CD30 monoclonal antibody </li></ul><ul><li>Primary endpoint: overall objective response rate (CR + PR) by independent review facility </li></ul><ul><li>Secondary endpoints: OS and PFS </li></ul>Chen R, et al. ASH 2010. Abstract 283. Brentuximab vedotin 1.8 mg/kg Administered every 21 days on outpatient basis over 30 min for a max of 16 cycles until at least SD achieved; patients restaged at cycles 2, 4, 7, 10, 13, 16 Follow-up every 12 wks Patients with relapsed/ refractory CD30+ disease, 12 yrs of age or older, measurable disease ≥ 1.5 cm, ECOG PS 0-1, previous ASCT (N = 102)
    45. 58. Brentuximab Vedotin (SGN-35) in Relapsed/Refractory HL: Results <ul><li>94% of patients achieved tumor reduction </li></ul><ul><li>Median treatment cycles: 9 (range: 1-16) </li></ul>Chen R, et al. ASH 2010. Abstract 283. Wks 70 0 10 20 30 40 50 60 Patients Free of PD or Death (%) 100 90 80 70 60 50 40 30 20 10 0 OS PFS per investigator PFS per IRF Median, Wks Not reached 39.1 25.1 Response, % Inv. IRF ORR 72 75 CR 33 34 PR 38 40 SD 27 22 PD 0 3 Not evaluable 1 1
    46. 59. Novel Therapies Under Investigation in Lymphomas
    47. 60. CAL-101 <ul><li>CAL-101: isoform-selective inhibitor of PI3K [1] </li></ul><ul><ul><li>Dosed at 50 mg BID up to 350 mg BID at 50-mg increments in a phase I trial in 55 patients with relapsed/refractory NHL </li></ul></ul><ul><ul><li>Partial responses seen at all doses </li></ul></ul><ul><ul><li>Grade ≥ 3 adverse events included neutropenia, lymphopenia, and thrombocytopenia </li></ul></ul>1. Kahl BS, et al. ASH 2010. Abstract 1777.
    48. 61. KW-0761 <ul><li>KW-0761: anti-CCXR4 monoclonal antibody </li></ul><ul><ul><li>Given at 1.0 mg/kg for 8 weekly infusions to 27 patients with relapsed T-cell lymphoma in a phase II trial </li></ul></ul><ul><ul><li>ORR: 14 patients (7 CR, 7 PR) </li></ul></ul>Ishida T, et al. ASH 2010. Abstract 285.
    49. 62. Conclusions <ul><li>1. Selected group of DLBCL patients may benefit from more aggressive treatment than standard R-CHOP chemotherapy </li></ul><ul><li>2. New agents are being evaluated for relapsed disease (conjugated monoclonal Abs and small molecule oral drugs) with promising results in early phase clinical trials </li></ul>
    50. 63. Thank You

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