Impacts of new agents for multiple myeloma on development of secondary myelodysplastic syndrome and acute myeloid leukemia.

The use of new agents (NAs) such as bortezomib, thalidomide, and lenalidomide has extended the survival of patients with multiple myeloma (MM). However, whether long-term treatment using NAs may increase the risk of second primary malignancies is a concern. Three hundred and thirty-three patients with MM were treated at our hospital from 1998 to 2013. Additional chromosomal abnormalities (CAs), associated with secondary myelodysplastic syndrome/acute myeloid leukemia, were observed in 13 of 152 users of NAs, but in 38 of 181 non-users of NAs. The cumulative CA incidence was higher in non-users of NAs. The CAs frequently observed were 13q-, 20q-, +8 in users of NAs, while -5/5q- and -7/7q- were detected in non-users of NAs. The total dose and treatment period of NAs did not differ between CAs-positive and -negative patients. However, a higher dose of melphalan was observed to have been used in patients who had CAs. Longer follow-up periods are necessary for an accurate risk assessment.

Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent.

BACKGROUND: Waldenström Macroglobulinemia (WM) is a rare subtype of indolent B-cell lymphoma, and prospective randomized studies on WM are scarce. The R-CHOP therapy [rituximab (R), cyclophosphamide, hydroxy-doxorubicin, vincristine, and prednisone] is a popular and recommended regimen for primary therapy, prescribed by several treatment guidelines for WM. However, treatment with R-CHOP is accompanied by severe myelosuppression and high rates of peripheral neuropathy. Therefore, we retrospectively evaluated the efficacy and toxicity of half-dose CHOP combined with R as a primary therapy for WM. METHODS: Patients with untreated symptomatic WM, treated at the Disaster Medical Center between April 2011 and September 2016, were retrospectively analyzed after administration of 6 cycles of half-dose R-CHOP for every 3 weeks. The response, median time to response, best response, progression-free survival, overall survival, and toxicities were evaluated. RESULTS: Of the 20 WM patients analyzed, 16 (80%) received half-dose R-CHOP without vincristine, and 13 (65%) responded to the treatment. With a median follow-up duration of 26.3 months, the 2-year progression-free survival and 2-year overall survival rates were 70 and 93.3%, respectively. The median time to response and best response were 6 and 9.9 weeks, respectively. Grade 3/4 leukocytopenia, neutropenia, febrile neutropenia, and Grade 1 peripheral neuropathy developed in 32, 37, 0, and 21% of patients, respectively. CONCLUSION: The half-dose R-CHOP is an effective and well-tolerated primary therapy for WM. To the best of our knowledge, this is the first study reporting the use of a reduced-dose R-CHOP regimen for the primary treatment of WM.