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Relapsed / refractory multiple myeloma: safety and clinical activity of Belantamab mafodotin with Pembrolizumab. DREAMM-4 study


Belantamab mafodotin ( Belamaf; Blenrep ), a B-cell maturation antigen ( BCMA ) targeted antibody-drug conjugate approved for adult patients with relapsed / refractory multiple myeloma, has a multimodal mechanism that eliminates myeloma cells via direct cytotoxicity and a systemic anti-tumor immune response, which may be augmented by an immune checkpoint inhibitor.
DREAMM-4 has assessed safety and clinical activity of Belamaf with Pembrolizumab ( Keytruda ) in relapsed / refractory multiple myeloma.

This was a phase I/II, single-arm, open-label study of adults with relapsed / refractory multiple myeloma after 3 or more lines of therapy ( LOT, including anti-CD38 monoclonal antibody, proteasome inhibitor, and immunomodulator ).

Part 1 established the dose of Belamaf 2.5 mg/kg with Pembrolizumab 200 mg, both IV Q3W up to 35 cycles, for the Part 2 expansion.

Primary efficacy endpoint was investigator-assessed overall response rate ( ORR, greater than or equal to partial response [ PR ] per IMWG criteria by investigator ).
Secondary endpoints included duration of response ( DoR ), progression-free survival ( PFS ), adverse events per NCI-CTCAE v4.03, and pharmacokinetics.

The primary analysis of all treated patients ( as of Oct 18, 2021 ) has included 34 patients ( 6 in Part 1 and 28 in Part 2 ).

In both parts, median prior LOT was 5 ( range 3–13 ); 10 patients ( 29% ) had high-risk cytogenetics and 9 ( 26% ) had extramedullary disease.

ORR was 47%, with most responses ( 10/16 patients ) very good partial response ( PR ) or better ( VGPR ).
Median follow-up was 14.7 months; median ( 95% CI ) DoR was 8.0 ( 2.1–not reached ) months; median PFS was 3.4 ( 1.4–5.6 ) months.

Most patients had 1 or more adverse events ( any grade [ Gr ]: 97%; Gr 3 or more: 74% ) and treatment-related adverse events ( TRAE, any Gr: 97%; Gr 3 or more: 65% ).
Most common ( 35% or more ) adverse events were keratopathy ( any Gr: 76%; Gr 3 or more: 38% ), vision blurred ( any Gr: 38%; Gr 3 or more: 0% ), and thrombocytopenia ( any Gr: 35%; Gr 3 or more: 29% ).

Adverse events led to dose delays ( 65% ) and dose reductions ( 32% ), but not discontinuation.

Nine patients had a serious adverse event ( SAE ); 4 patients had 1 or more SAE related to study treatment.

Two patients had immune-related adverse events of Gr 1 ( gout and autoimmune hypothyroidism ).

Preliminary pharmacokinetics and soluble BCMA data were consistent with single-agent Belamaf therapy.

In conclusion, Belamaf plus Pembrolizumab has demonstrated a favorable ORR compared with single-agent Belamaf in heavily pre-treated relapsed / refractory multiple myeloma.
No new TRAEs were identified; adverse events frequency and severity were similar to single-agent Belamaf. ( Xagena )

Suvannasankha A et al, J Clin Oncol 40, 2022 ( suppl 16; abstr 8018 )

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