ASH Community Perspectives on Non Hodgkin Lymphoma NHL

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					ASH 2009: Community Perspectives on
Non-Hodgkin's Lymphoma and Chronic
Lymphocytic Leukemia
 Moderator
 John Leonard, MD
 Professor of Medicine
 Weill Cornell Medical College
 New York, NY

 Faculty
 James Boyer, MD
 Martha Jefferson Hospital
 Charlottesville, Virginia

 Jack Jacoub, MD
 OC Blood and Cancer Care
 Orange Coast Memorial Medical Center
 Fountain Valley, California
Activity Goal

 • Assess key new findings and their clinical relevance in
   Non-Hodgkin's lymphoma (NHL; particularly follicular
   lymphoma, diffuse large B-cell lymphoma, and mantle
   cell lymphoma) and chronic lymphocytic leukemia
   (CLL)

 • Examine how these new findings may affect current
   clinical practice and discuss challenges to
   implementation of new practices in the community
   Follicular Lymphoma: Initial Therapy

     • Choice of initial therapy: B-R vs R-CHOP
         – B-R was well tolerated in a recent phase 3 trial
         – Progression-free survival benefit of at least 1 year was
           shown in patients who received B-R
     • How does B-R compare with CVP-R?
     • Is it too early to use B-R in clinical practice?



B-R = bendamustine and rituximab; R-CHOP = rituximab plus
cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP-R =
cyclophosphamide, vincristine, prednisone, and rituximab
Rummel MJ, et al. Blood. 2009;114:168. Abstract 405.
Follicular Lymphoma: Clinical Experience
With Bendamustine
 • Good experience in relapsed lymphomas
   – Very active and well tolerated
 • Some issues associated with dosing
 • Rapid adoption in the community setting
 • As a component of up-front treatment
   – For older patients but most likely not for young, fit patients
Follicular Lymphoma: Maintenance Therapy

 • Common to administer maintenance rituximab after
   initial induction therapy, even in the first-line setting
 • This approach is useful when the initial response to
   therapy is not optimal
 • Radioimmunotherapy consolidation is an alternative
 • What is the advantage of maintenance vs treatment
   at the time of progression?
   – Rituximab Extended Schedule or Retreatment Trial
     (RESORT) should provide needed information
   – Toxicity of long-term rituximab use is a concern
Follicular Lymphoma: Radioimmunotherapy
Consolidation
 • Not routinely used in the community and even in
   some academic centers
 • Can induce durable remissions
 • Secondary leukemia is a concern
 • May be most appropriate in the relapse setting in
   patients who have shorter remission, especially if
   older
 • Cost may be justified, but clinical cost (ie, leukemia
   risk) is a concern
   Mantle Cell Lymphoma

     • Limited randomized data to direct therapy
        – Intensive therapy appropriate for young, fit vs older
          patients; targeted agents for older patients
     • Innovative approaches needed
        – In patients with mantle cell lymphoma, progression-free
          survival with B-R was approximately 1 year longer than
          that with R-CHOPa
     • Drugs in development
        – Phosphoinositide-3 kinase inhibitors
        – Mammalian target of rapamycin inhibitors
        – Novel proteasome inhibitors


a. Rummel MJ, et al. Blood. 2009;114:168. Abstract 405.
   Large-Cell Lymphoma

     • CHOP-R-14 vs CHOP-R-21
         – Interim analysis of Groupe d'Etude des Lymphomes de
           l'Adulte (GELA) study in older patients with diffuse large B-
           cell lymphoma suggest that CHOP-R-14 may be inferior to
           CHOP-R-21
     • Community hematologists are waiting for an advance
       beyond the CHOP combination
         – Infusional regimens such as etoposide, prednisone,
           vincristine, and doxorubicin (EPOCH)?




Delarue R, et al. Blood. 2009;114:169. Abstract 406.
   Chronic Lymphocytic Leukemia: Up-Front
   Therapy
     • B-R is a newer choicea
         – Comparison with fludarabine-based therapy will be
           important because fludarabine has high toxicity
     • Other drug options are available depending on
       chromosomal makeup




a. Fischer K, et al. Blood. 2009;114:89. Abstract 205.
Therapies for Relapsed/Refractory
Chronic Lymphocytic Leukemia
 • Ofatumumab
   – Approved for use in fludarabine- and alemtuzumab-
     refractory CLL
   – Many community hematologists would consider
     bendamustine before alemtuzumab because of toxicity
   – Another treatment tool
 • Lenalidomide
   – High response rate in the refractory setting
   – More data needed, but yet another treatment option
Thank you for participating
in this activity.

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