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 nlBili < 2.0

Randomize

R-CHOP

Etanavir + R-CHOP

Results

Huang, Y-H, et al. J. Clin. Oncol. 31: 2765-2772, 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.