Denise Levitan

Lenalidomide after stem-cell transplantation for multiple myeloma

BACKGROUND Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. METHODS Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). RESULTS The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). CONCLUSIONS Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).

The Feasibility of Inpatient Geriatric Assessment for Older Adults Receiving Induction Chemotherapy for Acute Myelogenous Leukemia

To test the feasibility and utility of a bedside geriatric assessment (GA) to detect impairment in multiple geriatric domains in older adults initiating chemotherapy for acute myelogenous leukemia (AML).

Evaluation of the efficacy of the combination of oral bexarotene and methotrexate for the treatment of early stage treatment-refractory cutaneous T-cell lymphoma

Background: Various combination therapies are used in refractory cutaneous T-cell lymphoma (CTCL). Although bexarotene has been studied in combination with psoralen photochemotherapy (PUVA), IFN-α and denileukin difitox, there have been no published data assessing the efficacy of the combination of bexarotene and methotrexate. Objective: To evaluate the efficacy and safety of an oral bexarotene and methotrexate combination for the treatment of refractory CTCL. Method: A retrospective study was carried out of 12 patients with refractory stage CTCL treated with an oral combination of bexarotene and methotrexate from 2000 to 2007. Results: Twelve patients with CTCL stage IA–IIB disease who received a combination of bexarotene and methotrexate were identified. The median dose of bexarotene was 150 mg/day (range 75–300 mg/day) and methotrexate 15 mg/week (range 5–30 mg/week). The duration of time to achieve an overall response was 6.5 months (range 3–11 months). The overall response occurred in 66% (8/12). One patient had complete response (CR = 8%) and seven had partial response (PR = 58%). Six of 12 patients progressed at some point during treatment and needed additional intervention. Tolerance to the treatment was good and commonly observed side effects were hyperlipidemia, elevated liver transaminases and a decreased white blood cell count. Limitations of the study included a restricted number of patients, relatively short evaluation times and retrospective analysis. Conclusion: An oral bexarotene and methotrexate combination may be a promising future alternative to monotherapy for the treatment of CTCL, but further studies are required.

Arsenic trioxide during consolidation for patients with previously untreated low/intermediate risk acute promyelocytic leukaemia may eliminate the need for maintenance therapy

Aa total of 105 patients (age ≥18 years) with newly diagnosed low or intermediate risk acute promyelocytic leukaemia (APL) were treated with a standard induction and consolidation regimen including arsenic trioxide (ATO). Sixty‐eight patients who were polymerase chain reaction (PCR) negative for PML‐RARA post‐consolidation were randomized to either 1 year of maintenance with tretinoin, mercaptopurine and methotrexate, or observation. Enrollment in this non‐inferiority trial was stopped prematurely due to slow accrual. With a median follow up of 36·1 months, the overall survival of the 105 patients was 93%, and there have been no relapses in the patients randomized to maintenance or observation. These results demonstrate that cures can be expected in >90% of patients with low and intermediate risk APL and suggest that maintenance therapy may not be needed if patients are treated with an intensive post‐remission regimen including ATO. This trial was registered at clinicaltrials.gov as #NCT00492856.

Possible Role of Engraftment Syndrome and Autologous Graft-Versus-Host Disease in Myelodysplastic Syndrome After Autologous Stem Cell Transplantations: Retrospective Analysis and Review of the Literature

BACKGROUND We report a retrospective study of 452 patients with lymphoma from 1991 to 2006, with 274 men and 178 women, median age of 50 years (range, 16-76 years). PATIENTS AND METHODS There were 85 patients with Hodgkin lymphoma (HL) and 367 with non-Hodgkin lymphoma (NHL). Eleven patients received a second autologous transplantation for progressive lymphoma, and another 4 received a second allogeneic transplantation for myelodysplastic syndrome (MDS). Twenty-seven patients had skin biopsies, and 2 patients had gastrointestinal biopsies consistent with graft-versus-host disease (GVHD), and 11 patients developed severe engraftment syndrome (ES), as defined by noninfectious fever and skin rash with or without pulmonary infiltrates requiring systemic steroids. RESULTS The median follow-up of the patients was 6.2 years, and median overall survival was 5.3 years. Twenty-four patients (5.3%) developed MDS with median time of onset of 4.2 years (range, 8 months to 7.5 years). An additional 5 patients developed clonal karyotypic abnormalities in the bone marrow without clinical MDS. Actuarial probabilities of developing MDS at 5 and 8 years after transplantation were 5% and 15%, respectively. CONCLUSION The incidences of MDS are similar in HL and NHL. Multivariate analysis revealed older age, occurrence of ES/GVHD, and longer intervals between the initial diagnoses to transplantation as independent factors. It is conceivable that perturbation to the host immunity caused by either previous chemotherapy or conditioning regimens in the elderly might play a role in the development of MDS after autologous transplantation.

Two case reports of MDS with chromosome 7 abnormalities after treatment of AIDS-related Burkitt lymphoma occurring in patients on HAART therapy.

e18561 Background: Burkitt lymphoma (BL) follows a rapidly progressive course, in both HIV infected and non-infected patients (pts). Non-HIV infected pts fare better with multiagent, dose intensive regimens. The role of these regimens in HIV infected pts remains unclear, particularly in the era of HAART therapy. METHODS This is an observational case report. RESULTS Case 1: 37yo HIV+ male diagnosed with Stage IIIE BL by rectal mass biopsy. Bone marrow, and CSF were negative. He was treated according to CALGB 10002. HAART was continued during therapy with good control of HIV viremia. He achieved a CR. He developed progressive cytopenias. Bone marrow 6 months after completing therapy was consistent with MDS. FISH for 7q- was positive in 15.5% of cells. The pt underwent RIC sibling donor stem cell transplant. Despite engraftment, the patient developed AML 2 months after his transplant. The patient elected not to receive induction therapy and died 2 months later due to complications of AML. Case2: 41 year old HIV+ female diagnosed with Stage IV BL by liver biopsy. She was treated according to CALGB 10002. HAART therapy was given, but despite multiple combinations the patient had persistently detectable HIV viral load. CR was achieved. She remained cytopenic after completion of chemotherapy. Bone marrow biopsy 4 months after chemotherapy showed monosomy 7 by FISH in 20% of cells, without increased blasts. The pt had ongoing CMV and HIV viremia, therefore no therapy for MDS was given. Her BL recurred one month later. She entered hospice, and died of complications of BL. CONCLUSIONS We report 2 cases of tMDS with chromosome 7 abnormalities occurring after concurrent HAART and aggressive chemotherapy for AIDS related BL. This limited series raises concern that there may be a potential interaction of HAART and chemotherapy causing increased risk of MDS. One hypothesis is that mitochondrial damage, which has been reported from nucleoside analogue antiretrovirals, could lead to increased reactive oxygen species, which could further increase the known risk of tMDS in pts treated with dose intense regimens for BL.