Targeted Treatment of Relapsed or Refractory Follicular Lymphoma: Focus on the Therapeutic Potential of Mosunetuzumab

Figures & data

Figure 1 Timeline of the approval and withdrawal of the agents for the treatment of relapsed and refractory follicular lymphoma.

Table 1 Main Studies Involving Mosunetuzumab and the Approved Agents for the Treatment of Relapsed/Refractory Follicular Lymphomas

Treatment	Phase	Number of Patients	Overall Response Rate	Complete Response Rate	Reference
Mosunetuzumab	II	90	80%	60%	Budde^Citation24
Tisagenlecleucel	II	94	86.2%	69.1%	Fowler^Citation12
Axicabtagene ciloeucel	II	84	94%	79%	Jacobson^Citation13
Copanlisib	II	104	58.7%	20.2%	Dreyling^Citation33
Copanlisib + Rituximab	III	156	85%	37%	Matasar^Citation34
R2	III	147	80%	35%	Leonard^Citation35
R2	III	159	70%	41%	Andorski^Citation36
Tazemetostat	II	99 (45 EZH2^mut)	50% (69% EZH2^mut)	8% (13% EZH2^mut)	Morschhauser^Citation37
Tazemetostat + R2	Ib	41	97.6%	51.2%	Batlevi^Citation38
SC Mosunetuzumab	I/II	11	82%	64%	Budde^Citation39
Mosunetuzumab + Lenalidomide	I	27	92%	77%	Morschhauser^Citation40

Abbreviations: SC, subcutaneous; R2, rituximab + lenalidomide.

Table 2 Main Ongoing Trials Evaluating Mosunetuzumab in Follicular Lymphoma

NCT Number	Disease (No. of Previous Lines)	Treatment	Phase	Status
NCT04792502	FL or MZL (0)	Mosunetuzumab + Lenalidomide	II	Recruiting
NCT04712097	FL (≥1)	Mosunetuzumab + Lenalidomide	III	Recruiting
NCT05169515	NHL (≥1)	SC Mosunetuzumab or Glofitamab + CC-220 and CC99282	I	Recruiting
NCT02500407	NHL and CLL (≥1 and no other available therapy)	Mosunetuzumab + Atezolizumab	I/II	Active, not recruiting
NCT05410418	FL (0)	Mosunetuzumab + Polatuzumab vedotin	II	Recruiting
NCT05169658	FL or MZL (0)	Mosunetuzumab + Polatuzumab vedotin + Obinutuzumab	II	Recruiting
NCT04246086	FL (≥1)	SC or IV Mosunetuzumab + Lenalidomide	I/II	Recruiting
NCT03671018	NHL (≥1)	Mosunetuzumab + Polatuzumab vedotin	I/II	Recruiting
NCT03677141	NHL (≥1)	Mosunetuzumab + CHOP or CHP-Polatuzumab vedotin	I/II	Active, not recruiting
NCT05315713	FL or DLBCL (≥2)	Mosunetuzumab + Tiragolumab + Atezolizumab	I/II	Recruiting

Abbreviations: FL, follicular lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; DLBCL, diffuse large B-cell lymphoma; IV, intravenous; SC, subcutaneous; CHOP, cyclophosphamide, adriamycin, vincristine, prednisone; CHP, cyclophosphamide, adriamycin, prednisone.

Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055–1065. doi:10.1016/S1470-2045(22)00335-7

 PubMed Web of Science ®Google Scholar

Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the Phase 2 ELARA trial. Nat Med. 2022;28(2):325–332. doi:10.1038/s41591-021-01622-0

 PubMed Web of Science ®Google Scholar

Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91–103. doi:10.1016/S1470-2045(21)00591-X

 PubMed Web of Science ®Google Scholar

Dreyling M, Santoro A, Mollica L, et al. Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study. Am J Hematol. 2020;95(4):362–371. doi:10.1002/ajh.25711

 PubMed Web of Science ®Google Scholar

Matasar MJ, Capra M, Özcan M, et al. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, Phase 3 trial. Lancet Oncol. 2021;22(5):678–689. doi:10.1016/S1470-2045(21)00145-5

 PubMed Web of Science ®Google Scholar

Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: a Phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. JCO. 2019;37(14):1188–1199. doi:10.1200/JCO.19.00010

 PubMed Web of Science ®Google Scholar

Andorsky DJ, Coleman M, Yacoub A, et al. MAGNIFY phase IIIb interim analysis of induction R2 followed by maintenance in relapsed/refractory indolent NHL. JCO. 2020;38(15_suppl):8046. doi:10.1200/JCO.2020.38.15_suppl.8046

 Web of Science ®Google Scholar

Morschhauser F, Tilly H, Chaidos A, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020;21(11):1433–1442. doi:10.1016/S1470-2045(20)30441-1

 PubMed Web of Science ®Google Scholar

Batlevi CL, Salles G, Park SI, et al. Tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma: phase 1b results of symphony-1. Blood. 2022;140(Supplement1):2296–2298. doi:10.1182/blood-2022-166991

 Google Scholar

Budde E. Subcutaneous mosunetuzumab is active with a manageable safety profile in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs): updated results from a phase I/II study. ASH; 2022. Available from: https://ash.confex.com/ash/2022/webprogram/Paper157729.html. Accessed December 1, 2022.

 Google Scholar

Morschhauser F, Bishton M, Eyre TA, et al. Mosunetuzumab in combination with lenalidomide has a manageable safety profile and encouraging activity in patients with relapsed/refractory follicular lymphoma: initial results from a phase Ib study. Blood. 2021;138(Supplement 1):129. doi:10.1182/blood-2021-145694

 Google Scholar