-
Alison J Moskowitz, Paul A Hamlin,
Miguel-Angel Perales,
John Gerecitano,
Steven M Horwitz,
Matthew J Matasar,
Ariela Noy,
Maria Lia Palomba,
Carol S Portlock,
David J Straus,
Tricia Graustein,
Andrew D Zelenetz,
Craig H Moskowitz
[show abstract]
[hide abstract]
ABSTRACT: PURPOSELimited data exist regarding the activity of bendamustine in Hodgkin lymphoma (HL). This phase II study evaluated the efficacy of bendamustine in relapsed and refractory HL. PATIENTS AND METHODS
Patients with relapsed and refractory HL who were ineligible for autologous stem-cell transplantation (ASCT), or for whom this treatment failed, received bendamustine 120 mg/m(2) as a 30-minute infusion on days 1 and 2 every 28 days with growth factor support. The primary end point was overall response rate (ORR). A secondary end point was referral rate to allogeneic stem-cell transplantation (alloSCT) for patients deemed eligible for alloSCT at the time of enrollment.ResultsOf the 36 patients enrolled, 34 were evaluable for response. Patients had received a median of four prior treatments, and 75% had relapsed after ASCT. The ORR by intent-to-treat analysis was 53%, including 12 complete responses (33%) and seven partial responses (19%). The response rate among evaluable patients was 56%. Responses were seen in patients with prior refractory disease, prior ASCT, and prior alloSCT; however, no responses were seen in patients who relapsed within 3 months of ASCT. The median response duration was 5 months. Five patients (20% of those eligible) proceeded to alloSCT after treatment with bendamustine. Grade ≥ 3 adverse events were infrequent and most commonly included thrombocytopenia (20%), anemia (14%), and infection (14%). CONCLUSION
This study confirms the efficacy of bendamustine in heavily pretreated patients with HL. These results support current and future studies evaluating bendamustine combinations in relapsed and refractory HL.
Journal of Clinical Oncology 12/2012; · 18.37 Impact Factor
-
John Gerecitano,
Carol Portlock, Paul Hamlin,
Craig H Moskowitz,
Ariela Noy,
David Straus,
Philip Schulman,
Otilia Dumitrescu,
Debra Sarasohn,
Jennifer Pappanicholaou,
Alexia Iasonos,
Zhigang Zhang,
Qianxing Mo,
Endri Horanlli,
Celeste N Rojas,
Andrew D Zelenetz,
Owen A O'Connor
[show abstract]
[hide abstract]
ABSTRACT: To determine the safety and efficacy of substituting weekly or twice-weekly bortezomib for vincristine in the R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen in patients with relapsed/refractory indolent and mantle cell lymphoma (MCL).
Of the 57 patients in this phase I trial, 55 participated in 1 of 2 dosing schedules that included rituximab (375 mg/m(2)) and cyclophosphamide (750 or 1,000 mg/m(2)) administered on day 1 of each 21-day cycle and prednisone (100 mg orally) days 2 to 6. In the once-weekly schedule, bortezomib was administered on days 2 and 8; on the twice-weekly schedule, bortezomib was given on days 2, 5, 9, and 12. Bortezomib and cyclophosphamide were alternately escalated. A separate cohort of 10 patients in the twice-weekly schedule received concurrent pegfilgrastim (PegG) on day 2.
Both schedules of R-CBorP (rituximab, cyclophosphamide, bortezomib, and prednisone) were well tolerated. Most toxicities across all dose levels and cycles were grade 1 or 2. The overall response rates for patients on the weekly (n = 13) and twice-weekly (n = 33) schedules were 46% [23% complete response/complete response unconfirmed (CR/CRu)] and 64% (36% CR/CRu), respectively. Concurrent PegG did not increase hematologic toxicities in this regimen. A randomized phase II study is under way to further compare toxicity and efficacy of the 2 dosing schedules.
R-CBorP is a safe and effective regimen in patients with relapsed/refractory indolent and MCLs. Most toxicities were grade 1 or 2, and a promising response rate was seen in this phase I study.
Clinical Cancer Research 02/2011; 17(8):2493-501. · 7.74 Impact Factor
-
Paul A Hamlin
Current Oncology Reports 11/2010; 12(6):355-7. · 2.55 Impact Factor
-
Craig H Moskowitz,
Heiko Schöder,
Julie Teruya-Feldstein,
Camelia Sima,
Alexia Iasonos,
Carol S Portlock,
David Straus,
Ariela Noy,
Maria L Palomba,
Owen A O'Connor,
Steven Horwitz,
Sarah A Weaver,
Jessica L Meikle,
Daniel A Filippa,
James F Caravelli, Paul A Hamlin,
Andrew D Zelenetz
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE In studies of diffuse large B-cell lymphoma, positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. PATIENTS AND METHODS From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. RESULTS At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.
Journal of Clinical Oncology 03/2010; 28(11):1896-903. · 18.37 Impact Factor
-
Paul A Hamlin
Current Oncology Reports 10/2009; 11(5):329-30. · 2.55 Impact Factor
-
Paul A Hamlin
Current Oncology Reports 10/2008; 10(5):391-2. · 2.55 Impact Factor
-
Owen A O'Connor, Paul A Hamlin,
Carol Portlock,
Craig H Moskowitz,
Ariela Noy,
David J Straus,
Barbara Macgregor-Cortelli,
Ellen Neylon,
Debra Sarasohn,
Otila Dumetrescu,
Diane R Mould,
Martin Fleischer,
Andrew D Zelenetz,
Frank Sirotnak,
Steven Horwitz
[show abstract]
[hide abstract]
ABSTRACT: T-cell lymphomas (TCLs) are characterised by poor responses to therapy with brief durations of remissions. An early phase study of pralatrexate has demonstrated dramatic activity in patients with relapsed/refractory disease. Of the first 20 lymphoma patients treated, 16 had B-cell lymphoma and four had refractory aggressive TCL. All four patients with TCL achieved a complete remission. Patients with B-cell lymphoma achieved stable disease at best. For each TCL patient, the response was more durable than their best response with chemotherapy. This early experience is the first to document this unique activity of pralatrexate in TCL.
British Journal of Haematology 12/2007; 139(3):425-8. · 4.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Paraneoplastic cholestasis is an uncommon presenting symptom in Hodgkin's lymphoma (HL). Two distinct entities causing this clinical picture have been described: idiopathic cholestasis and vanishing bile duct syndrome (VBDS). We report a patient with idiopathic cholestasis and early-stage HL with favorable risk factors whose liver biopsy results were consistent with intrahepatic cholestasis and no ductopenia. Other causes for cholestatic jaundice were ruled out. He was treated with subtotal lymphoid irradiation and subsequently experienced a steady improvement in his liver function tests to near normal over 21 months. This case illustrates a rare paraneoplastic phenomenon, and a review of the available literature is included. We also discuss the differences between HL-related idiopathic cholestasis and VBDS. The distinction between these 2 diseases has prognostic implications: idiopathic cholestasis is usually reversible in early-stage HL after treatment, whereas patients who develop VBDS commonly die from their disease. There is no established approach to the management of paraneoplastic cholestasis. We postulate that single-modality radiation therapy alone should be considered a valid treatment alternative in early-stage HL with idiopathic cholestasis.
Clinical Lymphoma & Myeloma 08/2006; 7(1):77-82. · 1.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathological entity with unclear prognostic factors and optimal treatment approach. To elucidate an optimal treatment and identify predictive factors, a retrospective analysis of 141 consecutive patients was undertaken. Patients received cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone (CHOP)-like therapy, the non-Hodgkin lymphoma (NHL)-15 regimen or upfront autologous stem cell transplantation (ASCT) on Institutional Review Board approved trials or according to the institutional guidelines. Evaluation included lactate dehydrogenase, International Prognostic Index (IPI) assessment, computed tomography scan and gallium imaging. With a median follow-up of 10.9 years, event-free survival (EFS) and overall survival (OS) was 50% and 66% respectively. EFS/OS for CHOP/CHOP-like, NHL-15 and upfront ASCT was 34/51%, 60/84% and 60/78% respectively. CHOP/CHOP-like regimens had inferior EFS and OS versus NHL-15 or upfront ASCT (P < 0.001). A total of 23% of patients received radiotherapy. Multivariate analysis revealed the following outcome predictors: for EFS, greater than or equal to two extranodal sites and initial therapy received (NHL-15 or upfront ASCT); for OS, only initial therapy with NHL-15. We conclude: (i) dose-dense chemotherapy with NHL-15 may be superior to CHOP for PMLBL; (ii) The impact of consolidative radiotherapy requires randomised controlled trials; (iii) The age-adjusted IPI did not predict survival in this analysis; (iv) high-dose chemotherapy/ASCT should be reserved for upfront anthracycline-based therapy failure or in clinical trials for high-risk patients.
British Journal of Haematology 09/2005; 130(5):691-9. · 4.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A case of primary marginal zone B-cell lymphoma in an elderly female patient is presented. Primary breast lymphomas are rare, comprising less than 1 per cent of all breast malignancies. These tumors have no clinical, pathologic, or radiologic pathognomonic features to distinguish them from breast adenocarcinoma. The diagnosis is usually made with an excisional biopsy, and more extensive surgery should be avoided. Delivery of radiation therapy and chemotherapy is tailored according to the histologic grade, stage of disease, and overall patient condition. This report summarizes the current knowledge reflected in the literature.
The American surgeon 09/2004; 70(8):720-5. · 1.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Treatment options for patients with indolent non-Hodgkin's lymphoma historically involved radiation or chemotherapy. Although initial response rates are excellent, treatment is increasingly less effective with each successive relapse. The advent of immunotherapy heralds a new era for the treatment of these patients. Radioimmunotherapy adds the benefits of cytotoxic radiation to immunotherapy and represents a significant addition to the treatment armamentarium. Various antigens for lymphoma have been targeted, of which anti-CD20 antibodies are the furthest in development. Ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA), a (90)yttrium-labeled agent, and (131)iodine-labeled tositumomab (Bexxar; Corixa, Seattle, WA) are approved by the US Food and Drug Administration. Both agents have shown utility in therapy for relapsed and refractory low-grade and transformed lymphomas. This review highlights features of radioimmunotherapy that are relevant to non-Hodgkin's lymphoma, focusing on the two anti-CD20 antibodies.
Current Oncology Reports 10/2003; 5(5):364-71. · 2.55 Impact Factor
-
Paul A Hamlin,
Andrew D Zelenetz,
Tarun Kewalramani,
Jing Qin,
Jaya M Satagopan,
David Verbel,
Ariela Noy,
Carol S Portlock,
David J Straus,
Joachim Yahalom,
Stephen D Nimer,
Craig H Moskowitz
[show abstract]
[hide abstract]
ABSTRACT: Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P <.001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P <.001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens.
Blood 09/2003; 102(6):1989-96. · 9.90 Impact Factor
