Safety and Efficacy of Cd37‐targeting Naratuximab Emtansine Plus Rituximab in Diffuse Large B‐cell Lymphoma and Other Non‐hodgkin’s B‐cell Lymphomas – A Phase 2 Study

Levy, Moshe; Грудева-Попова, Жанет; Trněný, Marek; Jurczak, Wojciech; Pylypenko, Halyna; Jagadeesh, Deepa; André, Marc; Nasta, Sunita Dwivedy; Rechavi-Robinson, Dalit; Toffanin, Sara; Micallef, Sandrine; Attinger, Antoine; Rouits, Elisabeth; Dymkowska, Mariola; Nauwelaerts, Heidi; Woei-A-Jin, F J Sherida H

doi:10.1002/hon.156_2880

Cited by 5 publications

(8 citation statements)

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“…The phase III SEQUOIA trial assessed zanubrutinib as monotherapy and combination partner in treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) ≥ 65 years of age or unsuitable for FCR therapy (Figure 3). Results obtained for Arm C of the study already suggested efficacy and tolerability of single-agent zanubrutinib in patients with del(17p) [8,9]. Arms A and B of the SEQUOIA study compared zanubrutinib to BR in patients who did not have del(17p).…”

Section: Arms a And B Of The Sequoia Trialmentioning

confidence: 99%

“…Based on the ASCEND and ELE-VATE-RR trials, a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis assessed the quality-adjusted survival benefits of acalabrutinib versus the comparator agents [9]. The results reported at ASH 2021 indicated significant quality-adjusted survival benefit of acalabrutinib compared with idelalisib or bendamustine plus rituximab.…”

Section: Acalabrutinib: Ae and Q-twist Analysesmentioning

confidence: 99%

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A GLOBAL CONGRESS DIGEST ON TARGETED THERAPIES IN B-CELL MALIGNANCIES. Report from the American Society of Hematology (ASH) Annual Meeting, December 11–14, 2021

2022

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special issueduring treatment and until day 84 after the end of treatment; this was mostly due to infections. Fifteen deaths during the follow-up period were mostly due to secondary neoplasia. The rate of treatment discontinuation was low in all experimental arms. FCR plus ibrutinib in fit patientsIbrutinib-based treatment has been shown to prolong survival compared to FCR in CLL patients with unmutated IGHV [2]. It was hypothesized that combining ibrutinib with FCR (iFCR) as initial therapy would lead to high CR rates with uMRD in the bone marrow in a broad population of younger, fit CLL patients. The phase II study launched in 2014 enrolled a total of 85 patients at 7 US sites with a median age of 55 years. After a 1-week lead-in with ibrutinib alone, iFCR was administered for up to 6 cycles, followed by ibrutinib maintenance for 2 years. Patients who achieved uMRD at the end of this period discontinued therapy, while those who did not continued treatment until progression. Retreatment with ibrutinib was allowed in patients who relapsed. The primary endpoint of the trial was the CR rate with uMRD in the bone marrow 2 months after iFCR completion.According to the first analysis published in 2019, the primary endpoint was met after a median follow-up of 16.5 months, with 33 % of patients achieving CR as defined above [3]. The best uMRD rate in the bone marrow by intent-totreat (ITT) was 84 % at that time, which was higher than results obtained with any prior CIT or novel-agent-based regimen for initial CLL therapy.

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Section: Arms a And B Of The Sequoia Trialmentioning

confidence: 99%

Section: Acalabrutinib: Ae and Q-twist Analysesmentioning

confidence: 99%

A GLOBAL CONGRESS DIGEST ON TARGETED THERAPIES IN B-CELL MALIGNANCIES. Report from the American Society of Hematology (ASH) Annual Meeting, December 11–14, 2021

2022

memo

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“…In a phase I trial of 49 patients with relapsed/refractory B-cell NHL, naratuximab resulted in an ORR of 22% in the 18 patients with DLBCL (including a CR in one patient (6%)) [54]. A phase II study evaluated naratuximab in combination with rituximab in 100 patients with relapsed/refractory B-cell NHL, including 80 with DLBCL [55]. The most common grade ≥ 3 treatment-emergent adverse events were neutropenia (54%), lymphopenia (17%), and thrombocytopenia (11%).…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

“…The most common grade ≥ 3 treatment-emergent adverse events were neutropenia (54%), lymphopenia (17%), and thrombocytopenia (11%). In the 74 evaluable patients with DLBCL, the ORR and CR rates were 43 and 32%, respectively [55]. Zilovertamab vedotin is an MMAE-conjugated humanized IgG1 monoclonal antibody that targets ROR1, an oncofetal protein pathologically expressed in solid and lymphoid malignancies including DLBCL [56].…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies

Sawalha

2021

JPM

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Approximately 40% of patients with diffuse large B cell lymphoma (DLBCL) do not respond or develop relapsed disease after first-line chemoimmunotherapy. A minority of these patients can be cured with autologous hematopoietic stem cell transplantation (AHCT). Although chimeric antigen receptor (CAR) T cells have transformed the treatment paradigm of relapsed/refractory DLBCL, only 30–40% of patients achieve durable remissions. In addition, many patients with relapsed/refractory DLBCL are ineligible to receive treatment with CAR T cells due to comorbidities or logistical limitations. Since 2019, the following four non-CAR T-cell treatments have been approved in relapsed/refractory DLBCL: polatuzumab in combination with bendamustine and rituximab, selinexor, tafasitamab plus lenalidomide, and loncastuximab. In this article, I review the data behind these four approvals and discuss important considerations on their use in clinical practice. I also review emerging therapies that have shown promising early results in relapsed/refractory DLBCL including the bispecific antibodies, antibody–drug conjugates, Bruton tyrosine kinase inhibitors, BCL2 inhibitors, immune checkpoint inhibitors, and epigenetic modifiers.

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“…Naratuximab emtansine was evaluated in a phase I study (NCT01534715) in heavily pretreated RR NHL patients (median of three prior systemic regimens) and the results were encouraging with ORR 22% (4/18) in DLBCL cohort [ 46 ]. Based on these results, nara was selected for a phase II clinical trial in combination with rituximab for RR B-cell NHL patients (NCT02564744) [ 48 ]. Seventy-four RR DLBCL patients were evaluable for efficacy and ORR of 43.2% (32/74) with 32.4% (24/74) of CRs were observed in this group.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Promising Immunotherapeutic Modalities for B-Cell Lymphoproliferative Disorders

Mihályová

Hradská

Jelı́nek

et al. 2021

IJMS

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Over the last few years, treatment principles have been changed towards more targeted therapy for many B-cell lymphoma subtypes and in chronic lymphocytic leukemia (CLL). Immunotherapeutic modalities, namely monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cell therapy, commonly use B-cell-associated antigens (CD19, CD20, CD22, and CD79b) as one of their targets. T-cell engagers (TCEs), a subclass of bsAbs, work on a similar mechanism as CAR-T cell therapy without the need of previous T-cell manipulation. Currently, several anti-CD20xCD3 TCEs have demonstrated promising efficacy across different lymphoma subtypes with slightly better outcomes in the indolent subset. Anti-CD19xCD3 TCEs are being developed as well but only blinatumomab has been evaluated in clinical trials yet. The results are not so impressive as those with anti-CD19 CAR-T cell therapy. Antibody-drug conjugates targeting different B-cell antigens (CD30, CD79b, CD19) seem to be effective in combination with mAbs, standard chemoimmunotherapy, or immune checkpoint inhibitors. Further investigation will show whether immunotherapy alone or in combinatory regimens has potential to replace chemotherapeutic agents from the first line treatment.

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Safety and Efficacy of Cd37‐targeting Naratuximab Emtansine Plus Rituximab in Diffuse Large B‐cell Lymphoma and Other Non‐hodgkin’s B‐cell Lymphomas – A Phase 2 Study

Cited by 5 publications

References 0 publications

A GLOBAL CONGRESS DIGEST ON TARGETED THERAPIES IN B-CELL MALIGNANCIES. Report from the American Society of Hematology (ASH) Annual Meeting, December 11–14, 2021

A GLOBAL CONGRESS DIGEST ON TARGETED THERAPIES IN B-CELL MALIGNANCIES. Report from the American Society of Hematology (ASH) Annual Meeting, December 11–14, 2021

Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies

Promising Immunotherapeutic Modalities for B-Cell Lymphoproliferative Disorders

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