Nassoma King

A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low-grade B-cell lymphomas†

Bortezomib has demonstrated efficacy in patients with relapsed B‐cell non‐Hodgkin lymphoma (NHL) both alone and in combination with other agents; however, limited data exist regarding its toxicity in combination with common frontline therapies for indolent NHL. A phase 1 study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone (R‐CHOP) was conducted in patients with untreated follicular lymphoma (FL) and other indolent NHLs.

Vinorelbine, Paclitaxel, Etoposide, Cisplatin, and Cytarabine (VTEPA) Is an Effective Second Salvage Therapy for Relapsed/Refractory Hodgkin Lymphoma

BACKGROUND For Hodgkin lymphoma (HL) patients with refractory or relapsed (R/R) disease after primary therapy, the standard of care is a salvage regimen followed by autologous stem cell transplant (ASCT). However, patients who fail to respond to a salvage regimen have limited options. Our phase I study of cytarabine combined with fixed doses of vinorelbine, paclitaxel, etoposide, and cisplatin (VTEPA) for patients with R/R lymphoma showed an overall response rate (ORR) of 33%. PATIENTS AND METHODS To further examine the effectiveness of VTEPA, we conducted a retrospective review of 30 cases of R/R HL who received a salvage combination of VTEPA. RESULTS This population included 15 men (50%), 18 stage III/IV (60%), and 14 with an International Prognostic Score ≥3 (47%). The median number of previous regimens was 2 (range, 1-4), 19 patients (63%) received previous salvage therapy with ifosfamide, carboplatin, and etoposide. Twenty-seven patients were evaluable for response. The most common Grade 3/4 toxicities were pancytopenia (19 patients, 97%), nausea/vomiting (17, 57%), fatigue (14, 47%), and infection (6, 20%). Of the 27 patients evaluable for response, the ORR was 70% (7 complete response and 12 partial response). Twenty patients (66%) went on to ASCT and 1 patient underwent allogeneic transplant. With a median follow-up of 32 months, the median progression-free survival (PFS) and overall survival (OS) in patients who received transplantation after VTEPA were 28 and 38 months, respectively. CONCLUSION Treatment with VTEPA for R/R HL is feasible with manageable side effects. With a high ORR, the PFS and OS for this group of patients suggest that VTEPA is a promising regimen for HL patients in whom previous lines of therapy have failed.

Intensive chemotherapy and consolidation with high dose therapy and autologous stem cell transplant in patients with mantle cell lymphoma

Abstract Mantle cell lymphoma (MCL) remains incurable with conventional chemotherapy without consensus on the optimal initial treatment. We examined our single center experience with frontline therapy for patients with MCL in consecutive cases diagnosed 1995-2011. Among 81 patients, median age was 59 (28% were ≥ 65 years of age), 95% had stage III/IV disease and 54% had a low risk MCL International Prognostic Index score. Thirty-five percent (n = 28) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and 65% received R-HCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate/cytarabine; n = 53). Forty-one patients were consolidated with autologous stem cell transplant (ASCT). There were no significant differences in 2-year survival for R-CHOP versus R-HCVAD (p = 0.10) or for ASCT versus observation (p = 0.06). After controlling for clinical factors, R-HCVAD followed by ASCT was associated with superior progression-free survival (hazard ratio 0.26, 95% confidence interval 0.09–0.75).

Combination of GM-CSF With Fludarabine-Containing Regimens in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma

BACKGROUND Granulocyte-monocyte colony stimulating factor (GM-CSF) is a hematopoietic cytokine with immunomodulatory activity that has preclinical evidence for enhancement of antitumor immunity when administered in combination with chemotherapy. We evaluated the utility of GM-CSF with chemoimmunotherapy in patients with indolent non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) in a pilot study. PATIENTS AND METHODS Patients with previously untreated, relapsed, or refractory indolent NHL or CLL were treated with GM-CSF, rituximab, fludarabine, and cyclophosphamide or mitoxantrone for a maximum of 6 cycles. RESULTS Sixteen patients were enrolled, including 1 patient who did not receive study therapy. Of the 15 remaining patients, 6 received cyclophosphamide and 9 received mitoxantrone in combination with fludarabine, rituximab, and GM-CSF. The overall response rate for all patients was 87%. Nine patients have subsequently had relapse of their disease, and 6 remained in remission at last study contact. There were no toxic deaths during the study. CONCLUSION GM-CSF-based chemoimmunotherapy was well-tolerated and resulted in a high response rate and warrants evaluation in larger studies.