A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma

Brown, Jennifer R.; Messmer, Bradley T.; Werner, Lillian; Davids, Matthew S.; Mikler, Evgeny; Supko, Jeffrey G.; Fisher, David C.; LaCasce, Ann S.; Armand, Philippe; Jacobsen, Eric; Dalton, Virginia; Fernandes, Stacey M.; McDonough, Sean M.; Ritz, Jérôme; Rassenti, Laura Z.; Kipps, Thomas J.; Neuberg, Donna; Freedman, Arnold S.

doi:10.3324/haematol.2013.086207

Cited by 13 publications

(13 citation statements)

References 33 publications

(29 reference statements)

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“…It is a DNA-derived humanized IgG1 kappa mAb with a significant use in patients with genetically high-risk treatment-resistant CLL. [30] The subgroups that were hypothesized to benefit the most included patients with 17p deletion, bone marrow infiltration and refractory autoimmune cytopenia. [30,31] It received approval in the US for the first time in 2001 and was essentially reserved for patients with CLL who had received fludarabine therapy yet had progressive disease.…”

Section: Obinutuzumab (Ga101)mentioning

confidence: 99%

An update on newer monoclonal antibodies in lymphoma therapy

Kadavakolan

Puri

Sahay

et al. 2016

ASJO

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In 2014, an estimated 9.4% of all new cancers in the US were accounted to hematological cancers. Most of these cancers have a B-cell origin and on the cell surface express antigen CD20-known to restrict B-cells. Considering the intrinsic immune status of the patients receiving chemotherapy, monoclonal antibodies (mAbs) are designed to provide active or passive immunotherapy. Clinical success of rituximab-anti-CD20 mAb in the treatment of lymphoma has led to the development of newer generations of mAb to increase the anti-tumor activity. Hence, recent advances in lymphoma therapy are being built on the conventional prototype of anti-CD20 mAb-rituximab. Our review is an update on the advances in lymphoma therapy using mAb against CD20 including the second generation-ofatumumab, veltuzumab, ocrelizumab, and the third-generation mAbs-ocaratuzumab and obinutuzumab.

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Section: Obinutuzumab (Ga101)mentioning

confidence: 99%

An update on newer monoclonal antibodies in lymphoma therapy

Kadavakolan

Puri

Sahay

et al. 2016

ASJO

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“…In the relapsed setting, the management of patients with TP53 abnormalities is even more challenging. Several clinical studies have demonstrated that FCR and combinations with high-dose corticosteroids, alemtuzumab or alternative regimens consisting of rituximab, oxaliplatin, cytarabine and fludarabine (OFAR) have only limited and short-term efficacy and are associated with high toxicity rates 37–43 . However, depending on doses and application routes, it also seems feasible that alemtuzumab-based regimens can serve as a means to “bridge” the time to HSCT.…”

Section: The Unmet Need Of Poor Risk Cll Patients Before the Availabimentioning

confidence: 99%

“…To achieve a good remission state is however challenging, and as discussed before, some regimens that appear suitable come to the cost of high toxicities. Recent studies indicate that modified OFAR and alemtuzumab based regimens are the most favorable strategies to help prepare patients for successful HSCT by achieving good remissions 43,69–71 . In general, pre-transplant characteristics as assessed by the EBMT risk score seem to be of predictive value for OS: this score uses five patient-specific pre-transplant variables (age, disease status, time from diagnosis to transplant, donor type, and donor–recipient sex combination) 72 .…”

Section: Evidence For the Efficacy Of Hsct In Cllmentioning

confidence: 99%

Transplantation in Chronic Lymphocytic Leukemia

McClanahan

Gribben

2014

Hematology/Oncology Clinics of North America

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Article synopsis Allogeneic stem cell transplantation (HSCT) offers the only potentially curative approach to the treatment of chronic lymphocytic leukemia (CLL). However, this is applicable only to a minority of CLL patients in view of the advanced age at presentation. Moreover, HSCT is associated with significant treatment related mortality and morbidity, largely due to chronic graft versus host disease (GVHD). The judicious choice of which patients merit this approach therefore remains important. Internationally accepted guidelines suggest that HSCT is indicated in patients who are fit enough, have a suitable matched donor, have 17p deletion or TP53 mutations or have relapsed relatively quickly after chemo-immunotherapy. There are several new agents that are in clinical trials or recently approved in CLL that demonstrate impressive responses and durable durations of response in high risk patients who might be candidates for transplant. HSCT must always be considered in view of other, potentially less toxic therapies which could be offered. Therefore the choice of HSCT versus a novel agent is one that must be gauged on a patient by patient basis, and this will change as data mature on the use of these novel agents in CLL.

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“…rituximab [Brown et al 2010]. Although these patients were very heavily pretreated, with a median of four prior lines of therapy, the median OS of 47 months is the most encouraging of any nonrandomized alemtuzumab trial in the relapsed/refractory setting.…”

Section: Total Number Treated 817mentioning

confidence: 99%

“…As shown in Table 3, most of the larger trials have evaluated the combination of alemtuzumab with rituximab or with fludarabine. We identified 14 nonrandomized two-agent trials [Kennedy, 2002;Faderl et al 2003Faderl et al , 2010Nabhan et al 2004;Elter et al 2005;Pettitt et al 2006Pettitt et al , 2012Flowers et al 2007;Egle et al 2009Egle et al , 2010Brown et al 2010;Stilgenbauer et al 2010;Tedeschi et al 2011;Pospisilova et al 2012], three nonrandomized three-agent trials [Montillo et al 2011;Zent et al 2011;Elter et al 2012], one nonrandomized four-agent trial [Badoux et al 2011], and two randomized trials [Gribben et al 2005;Elter et al 2011]. In addition, UKCLL02 (Table 2) re-exposed 17 fludarabine-refractory patients (32% of the cohort) to fludarabine in combination with alemtuzumab [Varghese et al 2010].…”

Section: Delayed Toxicities and The Role Of Infection Prophylaxismentioning

confidence: 99%

Alemtuzumab use in relapsed and refractory chronic lymphocytic leukemia: a history and discussion of future rational use

Warner

Arnason

2012

Therapeutic Advances in Hematology

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Abstract:In this review, we outline the clinical experience with single-agent alemtuzumab as a treatment for relapsed and refractory chronic lymphocytic leukemia (CLL) in both prospective and retrospective trials and describe the multiagent use of the drug with the goal of updating clinicians on recent developments and possible future rational combinations. Alemtuzumab, an antibody targeting the lymphocyte-specific surface marker CD52, is an approved agent for the treatment of CLL. Despite its demonstrated efficacy, likely secondary to concerns regarding infectious complications, it is most commonly used in the relapsed and refractory setting. Given alemtuzumab's unique mechanism of action it has been demonstrated to have activity in disease that is refractory to both alkylating agents and purine analogs. Furthermore, it has activity in TP53-mutated disease, which has the worst prognosis of any subset of CLL. Alemtuzumab has greater efficacy on circulating disease relative to nodal disease. Rational combinations are attempting to use these attributes to increase response rates in patients with relapsed and refractory disease.

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A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma

Cited by 13 publications

References 33 publications

An update on newer monoclonal antibodies in lymphoma therapy

An update on newer monoclonal antibodies in lymphoma therapy

Transplantation in Chronic Lymphocytic Leukemia

Alemtuzumab use in relapsed and refractory chronic lymphocytic leukemia: a history and discussion of future rational use

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