Obinutuzumab for the First-Line Treatment of Follicular Lymphoma

Marcus, Robert; Davies, Andrew; Ando, Kiyoshi; Klapper, Wolfram; Opat, Stephen; Owen, Carolyn; Phillips, Elizabeth H; Sangha, Randeep; Schlag, Rudolf; Seymour, John F.; Townsend, William; Trněný, Marek; Wenger, Michael; Fingerle‐Rowson, Günter; Rufibach, Kaspar; Moore, Tom; Herold, Michael; Hiddemann, Wolfgang

doi:10.1056/nejmoa1614598

Cited by 601 publications

(647 citation statements)

References 19 publications

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“…8,9,20 Combined ofatumumab and bendamustine or CHOP has demonstrated high OR rates of 90% to 100% and CR rates of 62% to 67% in patients with untreated indolent non-Hodgkin lymphoma. However, several trials have examined novel anti-CD20 antibodies in combination with bendamustine or CHOP for newly diagnosed FL.…”

Section: Discussionmentioning

confidence: 99%

Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high‐risk follicular lymphoma: CALGB 50904 (Alliance)

Blum

Polley

Jung

et al. 2019

Cancer

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BACKGROUND: This multicenter, randomized phase 2 trial evaluated complete responses (CRs), efficacy, and safety with ofatumumab and bendamustine and with ofatumumab, bendamustine, and bortezomib in patients with untreated, high-risk follicular lymphoma (FL). METHODS: Patients with grade 1 to 3a FL and either a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2 with 1 lymph node >6 cm or an FLIPI score of 3 to 5 were randomized to arm A (ofatumumab, bendamustine, and maintenance ofatumumab) or to arm B (ofatumumab, bendamustine, bortezomib, and maintenance ofatumumab and bortezomib). RESULTS: One hundred twenty-eight patients (66 in arm A and 62 in arm B) received treatment. The median age was 61 years, and 61% had disease >6 cm; 29% had an FLIPI score of 2, and 71% had an FLIPI score of 3 to 5. In arm A, 86% completed induction, and 64% completed maintenance. In arm B, 66% and 52% completed induction and maintenance, respectively. Dose modifications were required in 65% and 89% in arms A and B, respectively. Clinically significant grade 3 to 4 toxicities included neutropenia (A, 36%; B, 31%), nausea/ vomiting (A, 0%; B, 8%), diarrhea (A, 5%; B, 11%), and sensory neuropathy (A, 0%; B, 5%). The estimated CR rates were 62% (95% confidence interval [CI], 50%-74%) and 60% (95% CI, 47%-72%) in arms A and B, respectively (P = .68). With a median follow-up of 3.3 years, the estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 80% and 97%, respectively, for arm A and 76% and 91%, respectively, for arm B. CONCLUSIONS: The CR rates, PFS, and OS were not improved with the addition of bortezomib to ofatumumab and bendamustine in patients with high-risk FL. Although grade 3 to 4 toxicities were similar, more patients treated with bortezomib required dose modifications and early discontinuation. Cancer 2019;125:3378-3389.

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Section: Discussionmentioning

confidence: 99%

Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high‐risk follicular lymphoma: CALGB 50904 (Alliance)

Blum

Polley

Jung

et al. 2019

Cancer

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“…41 There is emerging data demonstrating efficacy of obinutuzumab as a contemporary version of rituximab in desensitizing outpatients awaiting transplantation. 41 There is emerging data demonstrating efficacy of obinutuzumab as a contemporary version of rituximab in desensitizing outpatients awaiting transplantation.…”

Section: How S Hould Patients Underg O De S En S Itiz Ati On?mentioning

confidence: 99%

Desensitization in heart transplant recipients: Who, when, and how

Shah

Patel

2019

Clinical Transplantation

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The number of heart transplant candidates who have pre-formed antibodies against human leukocyte antigens (HLAs) is increasing over time. The purpose of this review is to discuss the process of antibody desensitization for heart transplant candidates. Specifically, we review the current status of antibody detection including identification, strength, and potential pathogenicity. We discuss which patients and when should they undergo desensitization therapies during heart transplant evaluation. Specific therapies including mechanical removal of antibodies, intravenous immunoglobulins, and novel immunosuppressive agents targeting antibody production will be discussed. Finally, future research strategies to develop novel desensitization therapies for heart transplant candidates will be reviewed. K E Y W O R D Sdesensitization, heart disease, sensitization

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“…MCL (mantle cell lymphoma) is a rare subtype of non-Hodgkin's B-cell lymphoma characterized by the translocation [11,14] with Cyclin D1 activation. MCL often shows an aggressive clinical course with poor prognosis.…”

Section: Btk Inhibitor Ibrutinibmentioning

confidence: 99%

“…The GALLIUM study was designed as a comparison of the efficacy and safety of obinutuzumab or rituximab plus chemotherapy followed by maintenance immunotherapy in previously untreated indolent NHL [11]. Obinutuzumab plus chemotherapy demonstrated a significantly reduced risk of progression or death relative to rituximab plus chemotherapy in FL (hazard ratio [HR] 0.66, 95% CI [confidence interval] 0.51-0.85 (p = 0.001).…”

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confidence: 99%

Recent Advances in Therapeutics for B-Cell Lymphoma

Terui¹

2018

JPP

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Abstract:Objectives: The molecular targeting drugs for the treatment of B-cell lymphoma have been dramatically developed. Recently, novel drugs of monoclonal antibodies and small molecules are approved by US FDA (Food and Drug Administration). Key Findings: This review summarizes characteristics, mechanisms, and results of the trials in the novel molecular targeting drugs for B-cell lymphoma such as obinutuzumab, polatuzumab vedotin, ibrutinib, idelalisib, and venetoclax. Summary: As a novel anti-CD20 antibody, obinutuzumab has been clinically developed on going. ADC (antibody drug conjugate) against CD79b molecules is also developed for B-cell lymphoma. BCR pathway is one of the most crucial pathways, and ibrutinib is a BTK (Bruton's tyrosine kinase) inhibitor that is under development for the treatment of B-cell malignancies, including CLL (chronic lymphocytic leukemia), MCL (mantle cell lymphoma), and DLBCL (diffuse large B-cell lymphoma), as well as FL (follicular lymphoma). BCL-2 family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax, which is a highly selective BCL-2 inhibitor, a mimic for its BCL2 homolog 3-domain to induce apoptosis, is also reported to be active against B-cell malignancies. Conclusions: Mechanism-based combination regimens including these drugs may be required in the future.

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Obinutuzumab for the First-Line Treatment of Follicular Lymphoma

Cited by 601 publications

References 19 publications

Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high‐risk follicular lymphoma: CALGB 50904 (Alliance)

Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high‐risk follicular lymphoma: CALGB 50904 (Alliance)

Desensitization in heart transplant recipients: Who, when, and how

Recent Advances in Therapeutics for B-Cell Lymphoma

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