Treatment of B Cell Malignancies: Current and Emerging Strategies Thomas A. Rado, MD, PhD

Treatment Strategy for a Heterogenous Group of Diseases  B cell malignancies can be low grade (indolent), intermediate grade or high grade (aggressive).  For each type of lymphoma use the least toxic therapy which is effective.  When possible, use the special characteristics of a lymphoma as a target for treatment.

Low Grade Lymphomas

Treatment of the Hepatitis B Patient With Lymphoma  Role of antiviral therapy (etanavir, 1 week before Cycle 1 to three months after Cycle 6): 80 patients: HBsAg – Anti-HBc Ab + AST < 2 x nl Bili < 2.0 Randomize R-CHOP Etanavir + R-CHOP

Results Huang, Y-H, et al. J. Clin. Oncol. 31: , 2013

Treatment of CLL/SLL and Follicular Lymphomas  These diseases cannot be cured.  “Watch and Wait” is a valid approach for asymptomatic patients.  Chemotherapy + Rituximab is superior to Chemotherapy alone regardless of regimen.  There is no clear evidence that adding “H” to R-COP is better than R-COP alone.

Old Regimens Still Work  Chlorambucil + Prednisone (now with Rituximab) is well tolerated. DFS is slightly shorter than with R-CHOP, but OS is the same. (Lister, TA, et al, Brit. Med. J. 1: 533, 1978; also, Peterson, BA, et al, J. Clin. Oncol. 21: 5, 2003).  Newest alkylating agent is Bendamustine. Highly effective, works with recurrent/refractory disease. Can use with prednisone and rituximab.

Old Regimens Still Work (2)  The “gold standard” was a combination of Fludarabine (a purine analog), Cyclophosphamide and Rituximab.  Rarely used today because of prolonged cytopenias and possible reduction in hematopoietic stem cells.

Newer Agents  Ofatumumab: Fully human monoclonal anti-CD20 antibody.  Higher affinity than rituximab, and no mouse sequences.  Ibrutinib: Inhibitor of Bruton Tyrosine Kinase.  Idelalisib: Inhibitor of Phospho-Inositol-3-Kinase; works well with rituximab.

Events at the B Cell Receptor

Ibrutinib and Idelalisib

High Grade B Cell Lymphomas  R-CHOP is still the gold standard. Use of an anthracycline is necessary.  For Primary Mediastinal B Cell Lymphoma more intense regimens, such as Dose Adjusted EPOCH-R, give higher CR and DFS rates. Localized XRT for bulky disease.

High Grade B Cell Lymphomas  Other regimens in widespread use: R-Hyper-CVAD, R-ICE, R-DHAP.  Especially useful relapsed or refractory disease.  Used to “clean out” the bone marrow before conditioning patient for autologous stem cell transplant.