Paul Hamlin

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (53)367.45 Total impact

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    ABSTRACT: High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HDT/ASCT) can improve survival in patients with lymphoma. Limited experience is available on the safety and efficacy of HDT/ASCT in elderly patients. In this article, we review the published data on the role of HDT/ASCT in management of lymphoma in older patients. Based on available data, evaluation of comorbidities, functional status, and comprehensive geriatric assessment (CGA) will help identify those who can benefit most from this intervention. Prospective clinical trials focusing on HDT/ASCT in older patients with lymphoma are needed to establish optimal management protocols in this select population.
    Current Oncology Reports 09/2015; 17(9):465. DOI:10.1007/s11912-015-0465-x · 2.89 Impact Factor

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    ABSTRACT: Abstract This study evaluated the safety and efficacy of inotuzumab ozogamicin (INO), a targeted humanized anti-CD22 antibody conjugated to calicheamicin, plus rituximab (R-INO) every 3 weeks, up to 6 cycles, followed by high dose therapy and autologous stem cell transplantation (HDT aSCT) in high-risk relapsed/refractory diffuse large B-cell (DLBCL) patients. The primary endpoint was overall response rate (ORR) after 3 cycles of R-INO. 63 patients were enrolled. Common grade 3/4 adverse events during R-INO treatment were thrombocytopenia, lymphopenia, and neutropenia. ORR after 3 cycles of R-INO was 28.6% (95% CI: 17.9-41.4). Eighteen patients underwent HDT-aSCT; 2-year PFS for these patients was 61.1%. Serious infections and hepatic toxicity following aSCT occurred in 33% and 22%, respectively. One- and 2-year PFS rates for all enrolled patients were 28.9% and 25.3%, respectively (median, 3.0 months). R-INO had lower than expected activity as a salvage regimen for transplant eligible patients with DLBCL.
    Leukemia and Lymphoma 02/2015; 56(10):1-27. DOI:10.3109/10428194.2015.1017821 · 2.89 Impact Factor
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    ABSTRACT: Background: Pre-transplantation 18F-fluorodeoxyglucose (FDG) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant (HDT/ASCT) for patients with relapsed or refractory Hodgkin's lymphoma. In this study, we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin, followed by augmented ifosfamide, carboplatin, and etoposide (ICE). Methods: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients with relapsed or refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen. All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin on days 1, 8, and 15 for two 28 day cycles. After completion of brentuximab vedotin treatment, patients received a PET scan. Patients who achieved PET-negative status (a Deauville score of 1 or 2) proceeded directly to HDT/ASCT; those with persistent abnormalities on PET received two cycles of augmented ICE (augICE; two doses of ifosfamide 5000 mg/m2 in combination with mesna 5000 mg/m2 continuous infusion over 24 h, days 1 and 2; one dose of carboplatin AUC 5, day 3; three doses of etoposide 200 mg/m2 every 12 h, day 1) before consideration for HDT/ASCT. Only patients with persistent abnormalities on PET after brentuximab vedotin received augICE; however, all patients in the intention-to-treat population were assessed for the primary outcome, which was the proportion of patients who were PET-negative after brentuximab vedotin alone or brentuximab vedotin followed by augICE. This study is registered with, number NCT01508312, and is no longer accruing patients. Findings: Between Jan 5, 2012, and Oct 4, 2013, we enrolled 46 patients. One patient was deemed ineligible, and not evaluable, before treatment initiation owing to having nodular, lymphocyte-predominant Hodgkin's lymphoma and thus 45 patients received treatment. After brentuximab vedotin, 12 patients (27%, 95% CI 13-40) were PET-negative and proceeded to HDT/ASCT. 33 (73%, 95% CI 60-86) patients were PET-positive after brentuximab vedotin; one PET-positive patient withdrew consent, therefore 32 PET-positive patients received augICE, 22 (69%, 95% CI 53-85) of whom were PET-negative. Overall, 34 patients (76%, 95% CI 62-89) achieved PET-negativity. All 44 patients who completed treatment as per protocol proceeded to receive HDT/ASCT. Brentuximab vedotin was well tolerated and associated with few grade 3-4 adverse events including hyperglycaemia (two [4%] patients, grade 3), nausea (one [2%], grade 3), hypoglycaemia (one [2%], grade 3 and one [2%], grade 4), and hypocalcaemia (one [2%], grade 3 and one [2%], grade 4). Interpretation: PET-adapted sequential salvage therapy with brentuximab vedotin followed by augICE resulted in a high proportion of patients with relapsed or refractory Hodgkin's lymphoma achieving PET-negativity, and therefore could optimise the chance of cure after HDT/ASCT. Funding: Seattle Genetics.
    The Lancet Oncology 02/2015; 16(3). DOI:10.1016/S1470-2045(15)70013-6 · 24.69 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a treatable and potentially curable malignancy that is increasing in prevalance in the elderly. Until recently, older patients with this malignancy were under-represented on clinical treatment trials, so optimal therapeutic approaches for these patients were generally exptrapolated from the treatment of younger patients with this disorder. Because of heightened toxicity concerns , older patients were sometimes given reduced dose therapy, potentially negatively impacting outcome. Geriatric considerations including functional status and comorbidities often were not accounted for in treatment decisions. Because of these issues as well as the lack of treatment guidelines for the elderly population, the International Society of Geriatric Oncology (SIOG) convened an expert panel to review DLBCL treatment in the elderly, and develop consensus guidelines for therapeutic approaches in this patient population. The following treatment guidelines address initial DLBCL therapy, in both limited and advanced stage disease, as well as approaches to the relapsed and refractory patient. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    Annals of Oncology 01/2015; 26(6). DOI:10.1093/annonc/mdv018 · 7.04 Impact Factor
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    ABSTRACT: We have prospectively studied a three month course of clarithromycin (substituted by Prevpac®, lansoprazole/ amoxicillin/ clarithromycin, in the first two wks when stool H pylori+) for non-bulky, advanced stage indolent lymphoma. These patients are often candidates for expectant monitoring and it is during this period that a window of opportunity may exist to identify and treat associated infections. Methods: All previously untreated patients with a new diagnosis of indolent lymphoma (FL and non-FL) meeting GELF criteria were treated with 12 weeks of clarithromycin. There were 32 evaluable patients, 4 of whom had stool H pylori. Results: At one month post-antibiotic therapy, we have observed lymphoma responses in 7 of 32 patients (21.9%). Two additional patients had objective response during followup (28.1% overall response). The median treatment free survival for antibiotic responders is 69.9 months and for non-responders, 30.6 months (p = 0.019). Conclusion: Three response patterns have been noted, perhaps suggestive of an immune-mediated response -- prompt PET negative; flair with delayed PET negative response; and gradual continuous improvement. This prospective study appears promising, may be a step toward developing a lymphoma prevention strategy by reducing “antigen drive,” and deserves further clinical/biological study.
    01/2015; 2(1). DOI:10.1515/tumor-2015-0001
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the elderly, and is increasing in incidence. Although significant therapeutic advances have recently been made in the care of older patients with DLBCL, based upon results of randomized clinical trials, many older patients are not eligible for such trials due to comorbidities and functional decline. Pre-treatment evaluation of older patients to ascertain potential tolerance to therapy is especially important in therapeutic decisions for this population. Evaluation by performance status alone is insufficient, especially in the elderly, and consideration of the impact of comorbidities and functional/social decline needs to be included in such assessment. As part of an International Society of Geriatric Oncology (SIOG) task force, the issues of prognosis, comorbidities, geriatric assessment, and supportive care measures in older patients with DLBCL will be reviewed, and recommendations for assessment and allied care made.
    Journal of Geriatric Oncology 12/2014; 6(2). DOI:10.1016/j.jgo.2014.11.004 · 1.86 Impact Factor
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    ABSTRACT: Background: The incidence of diffuse large B-cell lymphoma (DLBCL) occurs disproportionately in elderly patients. We evaluated real-world treatment patterns and outcomes in elderly DLBCL patients in the U.S. Materials and methods: A retrospective cohort analysis of 9,333 DLBCL patients from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was conducted. Patients were diagnosed between January 1, 2000, and December 31, 2007; were aged >66 years, and were continuously enrolled in Medicare Part A and B in the year prior to diagnosis. Within 3 months of diagnosis, 4,565 (49%) received rituximab plus chemotherapy (R+chemo), 2,181 (23%) received chemotherapy only, and 467 (5%) received rituximab monotherapy (R-mono). Cox proportional hazards regression assessed overall survival between R+chemo versus chemotherapy only and R-mono versus no treatment. Results: Overall, 23% of patients received no treatment, and the proportion was higher among those aged >80 years (33%). Patients receiving R+chemo were younger and more likely white compared with those receiving chemotherapy only. Patients receiving R-mono were older and more likely female compared with those not treated. In multivariate analysis, patients receiving chemotherapy only had a twofold increased mortality risk versus R+chemo, and this was confirmed in a subanalysis of patients aged >80 years. A 91% higher mortality risk was noted with receipt of fewer than six cycles versus six cycles of chemotherapy or chemoimmunotherapy. Patients receiving R-mono had a 69% decreased mortality risk compared with patients who were not treated. Conclusion: This real-world analysis of elderly DLBCL patients confirmed that 23% do not receive treatment. Overall survival is higher for patients receiving R+chemo and R-mono relative to chemotherapy only and no treatment, respectively. Suboptimal durations of therapy with curative intent (fewer than six cycles) were associated with poorer outcomes.
    The Oncologist 10/2014; 19(12). DOI:10.1634/theoncologist.2014-0113 · 4.87 Impact Factor
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    ABSTRACT: The standard treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in frail elderly patients has not been established. A variation was made on rituximab (R), cyclophosphamide (C), etoposide (E), procarbazine and prednisone (P), substituting vorinostat (V) for procarbazine. Patients ≥aged 60 years with relapsed/refractory DLBCL, not candidates for autologous stem cell transplantation, were treated R-CVEP [R 375 mg/m2 intravenously (IV), day 1; C 600 mg/m2 IV days 1, 8: E 70 mg/m2 IV day 1, 140 mg/m2 days 2, 3 orally (PO); V (300 vs. 400 mg) PO and P 60 mg/m2 PO days 1–10] every 28 d for six cycles. Quality of life (QoL) was assessed in addition to response. Thirty patients (median age 76 years, 69–88) were enrolled (one died before treatment). Maximum tolerated dose (MTD) for V was 300 mg. For 23 patients at MTD (six phase I + 17 phase II), two were discontinued for toxicity, one withdrew consent, eight achieved complete response (35%), five achieved partial response (22%) and seven progressed (25%). Median overall survival was 17·5 months. Median progression-free survival was 9·2 months. Nine patients are alive. QoL declined during treatment but improved above baseline for patients who completed treatment. In conclusion, R-CVEP was tolerated at MTD and produced durable responses with improved QoL.
    British Journal of Haematology 10/2014; 168(5). DOI:10.1111/bjh.13195 · 4.71 Impact Factor
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    ABSTRACT: Purpose: This first-in-human study evaluated the CD70-targeted antibody-drug conjugate SGN-75 in patients with relapsed or refractory CD70-positive non-Hodgkin lymphoma (NHL) or metastatic renal cell carcinoma (RCC). Methods SGN-75 was administered intravenously to 58 patients (39 RCC, 19 NHL) every 3 weeks (Q3Wk; doses escalated from 0.3 to 4.5 mg/kg) or on Days 1, 8, and 15 of 28-day cycles (weekly; doses of 0.3 or 0.6 mg/kg). Dose-limiting toxicities were evaluated during Cycle 1; treatment response was monitored every 2 cycles. Results: The maximum tolerated dose of SGN-75 in RCC patients was 3 mg/kg Q3Wk. Due to toxicity concerns (idiopathic thrombocytopenic purpura in 2 NHL patients treated weekly), dose escalation in the weekly schedule was terminated; no regimen was recommended for NHL patients. The most common adverse events reported in patients treated Q3Wk (N = 47) were fatigue (40%), dry eye (32%), nausea (30%), and thrombocytopenia (26%). The nadir for thrombocytopenia typically occurred during Cycle 1. Ocular adverse events (e.g., corneal epitheliopathy, dry eye) were reported for 57% of patients treated Q3Wk and were generally reversible. Antitumor activity in patients treated Q3Wk included 1 complete response, 2 partial responses, and 20 stable disease. SGN-75 exposures were approximately dose proportional, with a mean terminal half-life of 10 days. Substantial depletions of CD70-positive peripheral blood lymphocytes were observed after SGN-75 treatment. Conclusions: Modest single-agent activity and generally manageable adverse events were observed in heavily pretreated RCC and NHL patients. Administration Q3Wk was better tolerated than weekly dosing. Targeted ablation of CD70-positive lymphocytes was demonstrated.
    Investigational New Drugs 08/2014; 32(6). DOI:10.1007/s10637-014-0151-0 · 2.92 Impact Factor
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    ABSTRACT: High-dose therapy and autologous stem cell transplantation (HDT-ASCT) can offer potential long-term remission or cure in patients with non-Hodgkin lymphoma (NHL). Limited experience is available on the safety and efficacy of HDT-ASCT in elderly patients. This is a single-center, retrospective study examining outcomes of HDT-ASCT for 202 NHL patients age 60 years and older between January 2001 and December 2012. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age at HDT-ASCT, hematopoietic cell transplantation comorbidity index (HCT-CI), NHL histology, and remission status at the time of HDT-ASCT. The median age was 65 years (range 60-74) and the majority had either diffuse large B-cell lymphoma (DLBCL, n=73, 37%) or mantle cell lymphoma (MCL, n=69, 34%). One hundred and fifteen patients (57%) had high HCT-CI scores at the time of HDT-ASCT. With a median follow-up of 3.6 years (range 0.4-11.9 years) for survivors, PFS and OS at 3 years were 60% (95% CI: 53-68%) and 73% (95% CI: 67-80%), respectively. Transplant-related mortality (TRM) was 4% both at 100 days and at 1 year post HDT-ASCT. Age and HCT-CI score were not associated with OS or PFS, and high HCT-CI did not correlate with TRM. Seven patients (4%) developed secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) at a median of 35 months (range 6-48) post HDT-ASCT. In this single-center cohort of elderly patients with NHL undergoing HDT-ASCT, this intervention is proved tolerable and effective, with results similar to historic controls in younger patients. Our data suggest that age alone should not preclude HDT-ASCT in elderly patients.
    Biology of Blood and Marrow Transplantation 08/2014; 20(12). DOI:10.1016/j.bbmt.2014.08.019 · 3.40 Impact Factor
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    Tanya M Wildes · Valentin Goede · Paul Hamlin ·
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    ABSTRACT: Increasing age is both a risk factor for and a negative prognostic factor in lymphoid malignancies. The disparities in outcomes between older and younger adults with lymphoid malignancies may reflect age-related differences in treatment and in biology of disease. Lymphomas in older adults are biologically more aggressive. Only small age-related differences in the frequency of cytogenetic abnormalities are seen in multiple myeloma. No major differences in the biology of chronic lymphocytic leukemia (CCL) are seen across the age spectrum. Chemotherapy and immunotherapy in older adults with lymphoid malignancies are marked by greater vulnerability to toxicity of therapy. Excessive toxicity can result in poorer outcomes, either directly through treatment-related mortality, or through decreased dose intensity. Thus, new approaches to predict toxicity of therapy and stratified treatment algorithms based on risk of toxicity are needed. Herein we detail some of the promising approaches to predicting toxicity and tailoring treatment for older adults with lymphoid malignancies.
    05/2014; 34:e240-8. DOI:10.14694/EdBook_AM.2014.34.e240
  • Paul A Hamlin ·

    Journal of Clinical Oncology 05/2014; 32(17). DOI:10.1200/JCO.2014.55.2810 · 18.43 Impact Factor
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    Blood 05/2014; 123(18):2895-2897. DOI:10.1182/blood-2014-03-561878 · 10.45 Impact Factor
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    ABSTRACT: Peripheral T-cell lymphomas are aggressive lymphomas that have no standard treatment. Studies suggest that HD-ASCT in the first CR improves outcome. Few data exist regarding allo-HSCT in the first CR. We retrospectively identified patients (2001-2011) with PTCL-not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, initially treated with CHOP, CHOP-ICE (ifosfamide, carboplatin, etoposide), or other therapy with the intention to transplant in the first CR. Disease characteristics, therapy, progression-free survival (PFS), and OS were evaluated. Sixty-five patients were identified. PFS and OS were 38% and 52%, respectively, at 4 years. CHOP and CHOP-ICE regimens had similar outcomes. Treatment with allo-HSCT and HD-ASCT had OS at 4 years of 66% and 67%, respectively. Patients who did not proceed to transplant had OS of 27%. IPI score ≤ 2 and Prognostic Index for T-cell Lymphomas scores ≤ 1 predicted improved outcome. Combined analysis of interim response to CHOP and IPI score also predicted PFS and OS. Our results support consolidation of first CR with transplantation. The addition of etoposide did not improve outcomes. Baseline IPI and interim response to CHOP can predict outcomes and guide decisions about transplantation in first CR in PTCL. Randomized trials are necessary to confirm the efficacy of this approach.
    Clinical lymphoma, myeloma & leukemia 09/2013; 13(6). DOI:10.1016/j.clml.2013.07.005 · 2.02 Impact Factor
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    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; 31(4). DOI:10.1200/JCO.2012.45.3308 · 18.43 Impact Factor
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    ABSTRACT: We previously reported that remission duration < 1 year, extranodal disease, and B symptoms before salvage chemotherapy (SLT) can stratify relapsed or refractory Hodgkin lymphoma (HL) patients into favorable and unfavorable cohorts. In addition, pre-autologous stem cell transplant (ASCT) (18)FDG-PET response to SLT predicts outcome. This phase 2 study uses both pre-SLT prognostic factors and post-SLT FDG-PET response in a risk-adapted approach to improve PFS after high-dose radio-chemotherapy (HDT) and ASCT. The first SLT uses 2 cycles of ICE in a standard or augmented dose (ICE/aICE), followed by restaging FDG-PET scan. Patients with a negative scan received a transplant. If the FDG-PET scan remained positive, patients received 4 biweekly doses of gemcitabine, vinorelbine, and liposomal doxorubicin. Patients without evidence of disease progression proceeded to HDT/ASCT; those with progressive disease were study failures. At a median follow-up of 51 months, EFS analyzed by intent to treat as well as for transplanted patients is 70% and 79%, respectively. Patients transplanted with negative FDG-PET, pre-HDT/ASCT after 1 or 2 SLT programs, had an EFS of > 80%, versus 28.6% for patients with a positive scan (P < .001). This prospective study provides evidence that the goal of SLT in patients with Hodgkin lymphoma should be a negative FDG-PET scan before HDT/ASCT.
    Blood 12/2011; 119(7):1665-70. DOI:10.1182/blood-2011-10-388058 · 10.45 Impact Factor
  • Andrew S Epstein · Cyrus Hedvat · Fadi Habib · Paul Hamlin ·

    Clinical lymphoma, myeloma & leukemia 08/2011; 11(5):439-41. DOI:10.1016/j.clml.2011.06.013 · 2.02 Impact Factor
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    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. DOI:10.1158/1078-0432.CCR-10-1498 · 8.72 Impact Factor
  • Paul A Hamlin ·

    Current Oncology Reports 11/2010; 12(6):355-7. DOI:10.1007/s11912-010-0124-1 · 2.89 Impact Factor

Publication Stats

2k Citations
367.45 Total Impact Points


  • 2003-2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medicine
      • • Lymphoma Service
      New York, New York, United States
  • 2009
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
    • New York Presbyterian Hospital
      New York City, New York, United States