Citations

AbstractThis study examines the long‐term OS of relapsed AML patients who were enrolled to 9 successive ECOG‐ACRIN trials for newly diagnosed AML, during 1984‐2008. The objectives were to examine whether there is a trend of improvement in the survival of relapsed AML patients in the more recent studies and to search for prognostic factors that are associated with long‐term OS after relapse. A total of 3012 patients were enrolled, 1779 (59.1%) achieved CR1 and of these, 58.9% relapsed. The median follow‐up was 9.7 years. The median OS from relapse was 0.5 years and the 5‐year OS was 10 (±1)%. These results were similar even for the most recent studies. A multivariate model showed that age, cytogenetics at diagnosis, duration of CR1 and undergoing allogeneic transplantation were significantly associated with OS from relapse. Even among patients who relapsed with better prognostic factors; age < 40 and CR1 > 12 months, there was no significant OS difference between the studies. In conclusion, this large cohort appears to confirm that the survival of AML patients postrelapse continues to be dismal and has not improved during the past quarter of a century.

Purpose Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD ( P = .005), skin involvement ( P = .002), spleen ( P < .001), and liver ( P < .001), but not CNS ( P = .34), nodal involvement ( P = .94), and gingival hypertrophy ( P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.

BACKGROUNDIn an ECOG‐ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression‐free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long‐term follow‐up of the same patient cohort is presented.METHODSPatients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m2 × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities.RESULTSOf the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow‐up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10‐year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS.CONCLUSIONSWith long‐term follow‐up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B‐cell lymphoma. Cancer 2016;122:2996‐3004. © 2016 American Cancer Society.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti‐CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (≥ 65 years) patients (median age 76 years, n = 31) with treatment naïve progressive CLL. Patients received 8‐12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m2 weekly)(n = 16) or low dose (20 mg/m2 3x week)(n = 15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression‐free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti‐CD20 mAb therapy as a potentially more effective use of anti‐CD20 mAb in the treatment of CLL. Am. J. Hematol. 91:308–312, 2016. © 2015 Wiley Periodicals, Inc.

Key PointsIn a randomized phase 3 trial, overall response rates, PFS, and overall survival were similar between MPT-T and mPR-R. Toxicity with both regimens was common, but mPR-R was better tolerated, and patients on the mPR-R regimen reported better quality of life.