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Andrew D Zelenetz,
William G Wierda,
Jeremy S Abramson,
Ranjana H Advani,
C Babis Andreadis,
Nancy Bartlett,
Naresh Bellam,
John C Byrd,
Myron S Czuczman,
Luis E Fayad, [......],
Barbara Pro,
Nishitha Reddy,
Lubomir Sokol,
Lode Swinnen,
Christina Tsien,
Julie M Vose,
Joachim Yahalom,
Nadeem Zafar,
Mary A Dwyer,
Maoko Naganuma
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ABSTRACT: These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Non-Hodgkin's Lymphomas (NHL) and provide a discussion of the clinical evidence that support the updates. The updates discussed in this article feature recommendations for additional treatment options in patients with chronic lymphocytic leukemia and guidance surrounding the management of hepatitis virus reactivation/infections in high-risk patients with NHL undergoing antitumor therapy.
Journal of the National Comprehensive Cancer Network: JNCCN 03/2013; 11(3):257-273. · 4.41 Impact Factor
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ABSTRACT: PURPOSE: Based on prior reports suggesting a positive correlation between fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT and total sperm count and concentration, we sought to identify changes in testicular FDG uptake over the course of chemotherapy in young men with Hodgkin's lymphoma. METHODS: Fifty-two patients with a mean age of 24.2 years (range 15.5-44.4) at diagnosis monitored with FDG PET/CT to assess treatment response for Hodgkin's lymphoma were selected for this retrospective analysis under an Institutional Review Board waiver. Of the patients, 26 were treated with a chemotherapy regimen known to cause prolonged and sometimes permanent azoospermia (BEACOPP-bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) and 26 with a regimen known to have a much milder effect on gonadal function (ABVD-doxorubicin, bleomycin, vincristine, and dacarbazine). Each patient underwent one FDG PET/CT before treatment and at least one FDG PET/CT after start of chemotherapy. In all examinations, FDG activity was measured in the testes with different quantification metrics: maximum standardized uptake value (SUV(max)), SUV(mean), functional volume (FV) and total testicular glycolysis (TTG), and blood pool activity determined (SUV(mean)). RESULTS: Testicular FDG uptake (SUV(max)) was significantly associated with blood pool activity (p < 0.001). Furthermore, testicular FDG uptake metrics incorporating volume (e.g., FV and TTG) were associated with age. There was no significant change in SUV(max), SUV(mean), FV, and TTG from the PET/CT at baseline to the PET/CTs over the course of chemotherapy either for patients treated with BEACOPP or for patients treated with ABVD. CONCLUSION: For patients undergoing chemotherapy for Hodgkin's lymphoma, there is a significant association between testicular FDG uptake and blood pool activity, but no significant changes in FDG uptake over the course of chemotherapy. Therefore, FDG uptake may not be a feasible surrogate marker for fertility monitoring in patients with Hodgkin's lymphoma undergoing chemotherapy.
European Journal of Nuclear Medicine 02/2013; · 4.53 Impact Factor
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ABSTRACT: Abstract Background: We previously reported that (18)F fluoro-deoxy-glucose positron emission tomography scan (FDG-PET) is almost universally positive in patients with T cell lymphoma. In the current analysis we examined the impact of FDG-PET in the initial staging of peripheral T cell lymphomas (PTCL), and prognostic value of interim FDG-PET. Methods: This retrospective analysis identified patients with mature T or NK lymphomas who had PET scans as part of initial staging or staging at relapse [(N=95) (staging cohort)] in the peripheral T cell lymphoma (PTCL) database at Memorial Sloan-Kettering Cancer Center. A subset of these patients had repeat PET for interim restaging during initial therapy with curative intent [(N=50) (interim restaging cohort)]. Results: The frequency of specific T cell histologies included in this analysis were: PTCL not otherwise specified (NOS) (N=35); angioimmunoblastic T cell lymphoma (AITL) (N=17); anaplastic large cell lymphoma (ALCL), ALK-1+ (N=11) and ALK-1- (N=12); adult T cell lymphoma/leukemia (ATLL) (N=7); NK/T cell lymphoma (NKTCL) (N=10); enteropathy-associated T cell lymphoma (EATL) (N=3). In the staging cohort, 77 patients were newly diagnosed, 18 had relapsed disease. Pretreatment FDG-PET was positive in 96% of patients. PET identified additional disease sites in 47/95 patients (50%) when added to conventional staging. Most frequently identified additional sites were: other nodal (N=24); bone (N=10); skin (N=8); nasopharynx (N=4); spleen (N=3); and lung (N=2). However, FDG-PET modified CT-based staging in only 5/95 patients (5.2%): 2 patients were upstaged and 3 patients were downstaged. FDG-PET-based staging did not alter planned treatment for any patient. Interim restaging with PET was performed after a median of 4 cycles of chemotherapy. In this cohort, treatment regimens included CHOP (N=19); CHOP/ICE (N=24); other (N=7). Subsequently, 29 patients were consolidated with either autologous (N=22) or allogeneic (N=7) stem cell transplant. After a median follow up of 3.4 years for surviving patients, those with negative interim PET had superior progression free survival (PFS) compared to patients with positive interim PET (p 0.03). There were no differences in overall survival (OS). Conclusions: In PTCL, FDG-PET commonly identifies additional sites of disease but infrequently impact CT-based staging and does not influence therapy. Interim FDG-PET may predict for PFS. FDG-PET should be integrated into prospective trials to confirm these findings.
Leukemia & lymphoma 02/2013; · 2.40 Impact Factor
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Karim E Abou-Nassar,
Ann Vanderplas,
Jonathan W Friedberg,
Gregory A Abel,
Joyce Niland,
Maria A Rodriguez,
Myron S Czuczman,
Michael Millenson,
Allison Crosby,
Leo I Gordon, Andrew D Zelenetz,
Mark Kaminski,
Ann S Lacasce
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ABSTRACT: Abstract We describe the patterns of use of 18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the initial staging of patients with newly diagnosed grade 1-2 follicular lymphoma (FL) and its potential impact on treatment. Data were obtained from the National Comprehensive Cancer Network non-Hodgkin Lymphoma Outcomes Database. Patients who presented between January 1, 2001 and September 30, 2009 with newly diagnosed grade 1-2 FL, with at least 6 months of follow-up were included. We identified 953 eligible patients and 532 (56%) underwent FDG-PET as part of initial staging. Among patients who underwent FDG-PET for initial staging, 438 (82%) received early treatment compared to 259 (61.5%) of those staged without FDG-PET (p<0.0001). Of all stage 1 FL (n=100), 47% were treated with radiotherapy (RT) alone and the choice of initial treatment strategy for stage 1 FL did not vary significantly by use of FDG-PET (p=0.22). The use of FDG-PET for staging of FL is widespread and is associated with a greater proportion of patients receiving early therapy. Given the widespread use and high cost of FDG-PET, its clinical utility in stage 1 FL should be further evaluated.
Leukemia & lymphoma 01/2013; · 2.40 Impact Factor
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ABSTRACT: BACKGROUND: Rituximab has altered the treatment approach to B-cell malignancies and other diseases. Reports consider that rituximab had limited impact on serum immunoglobulins. However, anecdotes suggest that rituximab can cause symptomatic hypogammaglobulinemia. This retrospective study examined the relationship among rituximab, hypogammaglobulinemia, and treatment of symptomatic hypogammaglobulinemia with intravenous immune globulin (IVIG). METHODS: Patients with serial quantitative serum immunoglobulin (SIgG) concentrations before and subsequent to rituximab administration at Memorial Sloan-Kettering Cancer Center were identified. Information regarding rituximab administration, SIgG concentrations, frequency of infection, and administration of IVIG were recorded. RESULTS: Between December 1998 and April 2009, 211 patients with B-cell lymphoma treated with rituximab and with serial SIgG concentrations were identified. One hundred seventy-nine (85%) patients had normal SIgG before rituximab, 32 (15%) had low SIgG. After rituximab use, hypogammaglobulinemia was identified in 38.54% of patients with initially normal SIgG. The risk was greater in patients who received maintenance rituximab. Symptomatic hypogammaglobulinemia that prompted IVIG administration developed in 6.6% of patients. CONCLUSIONS: In this data set, rituximab administration was associated with a high frequency of hypogammaglobulinemia, particularly symptomatic hypogammaglobulinemia, among patients who received multiple courses of rituximab. Baseline and periodic monitoring of SIgGs is appropriate in patients who receive rituximab.
Clinical lymphoma, myeloma & leukemia 12/2012;
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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
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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; · 18.37 Impact Factor
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Andrew D Zelenetz,
William G Wierda,
Jeremy S Abramson,
Ranjana H Advani,
C Babis Andreadis,
Nancy Bartlett,
Naresh Bellam,
John C Byrd,
Myron S Czuczman,
Luis Fayad, [......],
Barbara Pro,
Nishitha Reddy,
Lubomir Sokol,
Lode Swinnen,
Christina Tsien,
Julie M Vose,
Joachim Yahalom,
Nadeem Zafar,
Maoko Naganuma,
Mary A Dwyer
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ABSTRACT: These NCCN Guidelines Insights summarize several key updates to the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas (NHL) and describe the clinical evidence supporting the updates. The featured updates include changes to the recommendations for treatment options in patients with chronic lymphocytic leukemia (including in elderly or frail patients and patients with poor-risk cytogenetics), guidance surrounding surveillance imaging for follow-up of patients with NHL, and the addition of first-line consolidation options for patients with mantle cell lymphoma.
Journal of the National Comprehensive Cancer Network: JNCCN 12/2012; 10(12):1487-1498. · 4.41 Impact Factor
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ABSTRACT: INTRODUCTION: Hepatosplenic T-cell lymphoma is a rare form of extranodal non-Hodgkin lymphoma, first recognized as a distinct entity in the Revised European-American Lymphoma classification. Typical presentation includes lymphomatous infiltration of spleen and liver, and peripheral lymphadenopathy is rarely seen. The prognosis is almost uniformly poor, and there are no prospective studies of treatment of HSTCL. PATIENTS AND METHODS: For this report, we conducted a retrospective review of all pts who underwent treatment for HSTCL at our institution. Individual chart review was performed to report clinical presentation, management, and outcome. RESULTS: We identified 14 pts with HSTCL managed at our center, 7 of which remain alive with median follow-up of 65.6 months. Six of 7 received alternative induction chemotherapy regimens such as ICE (ifosfamide, carboplatin, etoposide) or IVAC (ifosfamide, etoposide, high-dose cytarabine) as opposed to CHOP and all surviving pts had proceeded to undergo either autologous or allogeneic SCT. CONCLUSION: Our results suggest that use of non-CHOP induction regimen and early use of high dose therapy and SCT consolidation may translate to improved survival for pts with HSTCL.
Clinical lymphoma, myeloma & leukemia 10/2012;
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ABSTRACT: PURPOSE The optimal management of stage I follicular lymphoma, according to consensus guidelines, is based on uncontrolled experiences of select institutions. Diverse treatment approaches are used despite guidelines that recommend radiation therapy (XRT). PATIENTS AND METHODS We analyzed outcomes of patients with stage I follicular lymphoma enrolled onto the National LymphoCare database. Results Of 471 patients with stage I follicular lymphoma, 206 patients underwent rigorous staging as defined by both a bone marrow aspirate and biopsy and an imaging study (a computed tomography [CT] scan of the whole body, a positron emission tomography [PET]/CT scan, or both). Rigorously staged patients had superior progression-free survival (PFS) compared with nonrigorously staged patients (hazard ratio [HR], 0.63). Treatments given to rigorously staged patients were rituximab/chemotherapy (R-chemo; 28%), XRT (27%), observation (17%), systemic therapy + XRT (13%), rituximab monotherapy (12%), and other (3%). With a median follow-up of 57 months for PFS, there were 44 progression events (in 21% of patients) for rigorously staged patients. For these patients, PFS was significantly improved with either R-chemo or systemic therapy + XRT compared with patients receiving XRT alone after adjustment for histology, LDH, and the presence of B symptoms. There were no differences in overall survival. CONCLUSION In this largest, prospectively enrolled group of patients with stage I follicular lymphoma, variable treatment approaches resulted in similar excellent outcomes, which challenges the paradigm that XRT should be standard for this presentation.
Journal of Clinical Oncology 08/2012; 30(27):3368-75. · 18.37 Impact Factor
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Ann S LaCasce,
Jonathan L Vandergrift,
Maria A Rodriguez,
Gregory A Abel,
Allison L Crosby,
Myron S Czuczman,
Auayporn P Nademanee,
Douglas W Blayney,
Leo I Gordon,
Michael Millenson,
Ann Vanderplas,
Eva M Lepisto, Andrew D Zelenetz,
Joyce Niland,
Jonathan W Friedberg
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ABSTRACT: Few randomized trials have compared therapies in mantle cell lymphoma (MCL), and the role of aggressive induction is unclear. The National Comprehensive Cancer Network (NCCN) Non-Hodgkin Lymphoma (NHL) Database, a prospective cohort study collecting clinical, treatment, and outcome data at 7 NCCN centers, provides a unique opportunity to compare the effectiveness of initial therapies in MCL. Patients younger than 65 diagnosed between 2000 and 2008 were included if they received RHCVAD (rituximab fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone), RCHOP+HDT/ASCR (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone + high-dose therapy/autologous stem cell rescue), RHCVAD+HDT/ASCR, or RCHOP. Clinical parameters were similar for patients treated with RHCVAD (n = 83, 50%), RCHOP+HDT/ASCR (n = 34, 20%), RCHOP (n = 29, 17%), or RHCVAD+HDT/ASCR (n = 21, 13%). Overall, 70 (42%) of the 167 patients progressed and 25 (15%) expired with a median follow-up of 33 months. There was no difference in progression-free survival (PFS) between aggressive regimens (P > .57), which all demonstrated superior PFS compared with RCHOP (P < .004). There was no difference in overall survival (OS) between the RHCVAD and RCHOP+HDT/ASCR (P = .98). RCHOP was inferior to RHCVAD and RCHOP+HDT/ASCR, which had similar PFS and OS. Despite aggressive regimens, the median PFS was 3 to 4 years. Future trials should focus on novel agents rather than comparing current approaches.
Blood 03/2012; 119(9):2093-9. · 9.90 Impact Factor
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Craig H Moskowitz,
Matt J Matasar, Andrew D Zelenetz,
Stephen D Nimer,
John Gerecitano,
Paul Hamlin,
Steven Horwitz,
Alison J Moskowitz,
Ariela Noy,
Lia Palomba,
Miguel-Angel Perales,
Carol Portlock,
David Straus,
Jocelyn C Maragulia,
Heiko Schoder,
Joachim Yahalom
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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. · 9.90 Impact Factor
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Gregory A Abel,
Ann Vanderplas,
Maria A Rodriguez,
Allison L Crosby,
Myron S Czuczman,
Joyce C Niland,
Leo I Gordon,
Michael Millenson, Andrew D Zelenetz,
Jonathan W Friedberg,
Ann S LaCasce
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ABSTRACT: We aimed to characterize surveillance imaging and circumstances of relapse for patients with diffuse large B-cell lymphoma (DLBCL) in the National Comprehensive Cancer Network Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting clinical and outcome data at seven comprehensive cancer centers. Patients presenting with newly diagnosed DLBCL in remission ≥3 months after initial therapy and who had accrued 2 years of follow-up were eligible for analysis (n = 625). The median number of imaging studies was 2.5/year (institutional range 0.5-3.5, p < 0.0001); 48.4% received only dedicated computed tomography (CT) scans, 14.6% received only positron emission tomography (PET)-inclusive modalities, 32.8% received a combination and 4.2% received no imaging. Among all eligible patients, 50 (8.0%) experienced relapse, and approximately one-quarter of subclinical relapses were detected through routine imaging. Our results suggest that despite limited data regarding its effect on outcomes, surveillance imaging is prevalent in DLBCL, and a majority of patients receive PET scans at some point during follow-up.
Leukemia & lymphoma 11/2011; 53(6):1113-6. · 2.40 Impact Factor
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Anita Kumar,
Ann Vanderplas,
Ann S LaCasce,
Maria A Rodriguez,
Allison L Crosby,
Eva Lepisto,
Myron S Czuczman,
Auayporn Nademanee,
Joyce Niland,
Leo I Gordon,
Michael Millenson, Andrew D Zelenetz,
Jonathan W Friedberg,
Gregory A Abel
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ABSTRACT: Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. The objective of this study was to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy using the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at 7 participating centers.
Patients who were eligible for this analysis presented with newly diagnosed DLBCL between January 2001 and July 2008, had no evidence of baseline CNS disease, and had received R-CHOP within 180 days of diagnosis. The authors assessed incidence and covariates of prophylaxis, prophylaxis modality, and, using propensity score analysis, outcomes such as overall survival.
Of 989 eligible patients, 117 received CNS prophylaxis (11.8%), most intrathecally (71.8%). Involvement of bone marrow, other high-risk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis (all P < .0001). At a median follow-up of 2.5 years, there were 20 CNS recurrences (2% [95% confidence interval, 1.1%-2.9%]) among all patients, and overall survival was not affected by prophylaxis.
Given the overall low rate of CNS recurrence and lack of prophylaxis-associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era.
Cancer 10/2011; 118(11):2944-51. · 4.77 Impact Factor
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Jonathan H Schatz,
Elisa Oricchio,
Andrew L Wolfe,
Man Jiang,
Irina Linkov,
Jocelyn Maragulia,
Weiji Shi,
Zhigang Zhang,
Vinagolu K Rajasekhar,
Nen C Pagano,
John A Porco,
Julie Teruya-Feldstein,
Neal Rosen, Andrew D Zelenetz,
Jerry Pelletier,
Hans-Guido Wendel
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ABSTRACT: New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and the redundancy of oncogenic signaling pathways provides back-up mechanisms that allow cancer cells to escape. For example, the AKT and PIM kinases produce parallel oncogenic signals and share many molecular targets, including activators of cap-dependent translation. Here, we show that PIM kinase expression can affect the clinical outcome of lymphoma chemotherapy. We observe the same in animal lymphoma models. Whereas chemoresistance caused by AKT is readily reversed with rapamycin, PIM-mediated resistance is refractory to mTORC1 inhibition. However, both PIM- and AKT-expressing lymphomas depend on cap-dependent translation, and genetic or pharmacological blockade of the translation initiation complex is highly effective against these tumors. The therapeutic effect of blocking cap-dependent translation is mediated, at least in part, by decreased production of short-lived oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves. Hence, targeting the convergence of oncogenic survival signals on translation initiation is an effective alternative to combinations of kinase inhibitors.
Journal of Experimental Medicine 08/2011; 208(9):1799-807. · 13.85 Impact Factor
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ABSTRACT: Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years.
Journal of Oncology Practice 07/2011; 7(4):213-8.
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ABSTRACT: Radioimmunotherapy (RIT) with (90)Y-ibritumomab tiuxetan or (131)I-tositumomab combines a radiation-emitting radionuclide with an antibody targeting CD20 to treat B-cell non-Hodgkin lymphoma. Multiple studies demonstrate favorable RIT efficacy and safety profiles in follicular lymphoma (FL). The primary toxicity is reversible myelosuppression. Various FL treatment options include single-agent immunotherapy, radiation, chemoimmunotherapy, and RIT. Examining RIT clinical effects and position within treatment algorithms is important to optimal patient benefit. Clinical studies support using single-agent RIT in relapsed/refractory FL, in selected patients with new, untreated FL, and as consolidation after induction chemotherapy or chemoimmunotherapy. RIT as consolidation enhances response rates (with conversion of partial to complete responses following induction therapy) and prolongs disease control versus observation. The overall response rate is 60-80% in the relapsed setting. Time to progression is longer with low-bulk disease, fewer prior therapies, and retained rituximab sensitivity. RIT apparently does not preclude subsequent therapies or increase risk of secondary malignancies compared with chemotherapy's known risk. This article summarizes consensus recommendations for RIT and presents RIT treatment algorithms developed by hematologists/oncologists who regularly treat patients with FL. Maximizing RIT benefit requires healthcare providers to utilize algorithms assisting with treatment decisions.
Leukemia & lymphoma 07/2011; 52(7):1188-99. · 2.40 Impact Factor
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Andrew D Zelenetz,
Jeremy S Abramson,
Ranjana H Advani,
C Babis Andreadis,
Nancy Bartlett,
Naresh Bellam,
John C Byrd,
Myron S Czuczman,
Luis E Fayad,
Martha J Glenn, [......],
Oliver Press,
Barbara Pro,
Nashitha Reddy,
Lubomir Sokol,
Lode J Swinnen,
Christina Tsien,
Julie M Vose,
William G Wierda,
Joachim Yahalom,
Nadeem Zafar
Journal of the National Comprehensive Cancer Network: JNCCN 05/2011; 9(5):484-560. · 4.41 Impact Factor
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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
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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. · 7.74 Impact Factor
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Andrew D Zelenetz
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ABSTRACT: At the 52(nd) Annual Meeting and Exposition of ASH in December, some 881 abstracts included information on Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL), with at least 363 on chronic lymphocytic leukemia (CLL). This brief summary discusses some of the important findings that will begin to impact practice. Follicular Lymphoma Overall survival (OS) for patients with follicular lymphoma (FL) has improved since the introduction of rituximab. Data have shown that for patients who need treatment, rituximab added to chemotherapy improves overall response (OR) and complete response (CR) rates, progression-free survival (PFS), and OS.(1-4) In an update of the Primary RItuximab and MAintenance (PRIMA) trial, Salles et al.(5) enrolled patients with untreated, high tumor-burden FL. Patients were treated with 1 of 3 regimens (R-CHOP, R-CVP, or R-FCM) at the discretion of the treating physician. Patients with a partial response or CR were randomized to observation or maintenance with rituximab, 375 mg/m(2), once every 8 weeks for 2 years. At a median of 42 months after registration, the 36-month PFS was 75% in the maintenance arm versus 58% in the observation arm, which met the primary end point of a 45% improvement in median PFS. The only safety issue was a slight increase in risk of infection in the maintenance group. In a subanalysis of the PRIMA study, Trotman et al.(6) examined the role of FDG-PET imaging to predict outcome in FL. At diagnosis, 99% (119/120) of PET scans were positive, demonstrating their utility for initial diagnosis. Among 124 patients who underwent...
Journal of the National Comprehensive Cancer Network: JNCCN 01/2011; 9(1):7-11. · 4.41 Impact Factor
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ABSTRACT: To identify prognostic factors for patients transplanted for relapsed or refractory Hodgkin lymphoma we carried out a combined analysis of patients followed prospectively on 3 consecutive protocols at Memorial Sloan-Kettering Cancer Center. One hundred fifty-three patients with chemosensitive disease after ICE (ifosfamide, carboplatin, and etoposide)-based salvage therapy (ST) proceeded to high-dose chemoradiotherapy followed by autologous stem cell transplantation (ASCT). Patients were evaluated with computed tomography and functional imaging (gallium or fluorodeoxyglucose-positron emission tomography) prior to ST and again before ASCT. Functional imaging status before ASCT was the only factor significant for event-free survival (EFS) and overall survival by multivariate analysis and clearly identifies poor risk patients (5-year EFS 31% and 75% for FI-positive and negative patients respectively). Administration of involved-field radiotherapy with ASCT was marginally significant for EFS (P = .055). Studies evaluating novel STs, conditioning regimens, post-ASCT maintenance, or allogeneic stem cell transplantation are warranted for patients who fail to normalize pre-ASCT functional imaging.
Blood 12/2010; 116(23):4934-7. · 9.90 Impact Factor
