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Patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL) have limited treatment options, often resulting in poor outcomes. Bispecific antibodies that bind to both CD3 on T cells, and CD20 on malignant B cells have shown high response and complete remission rates in patients with R/R NHL. Glofitamab is an anti-CD20 and anti-CD3 bispecific antibody currently being investigated in a phase I dose-escalation trial (NCT03075696) for use in patients with R/R NHL. The Lymphoma Hub has previously reported preliminary results from this trial, and more recently interviewed one of the investigators, Carmelo Carlo-Stella, Humanitas University, Milan, IT, on how step-up dosing fared when compared with fixed dosing for glofitamab.
During the 26th Congress of the European Hematology Association (EHA2021), an e-poster on updated findings from the phase I dose-escalation trial (NCT03075696) of glofitamab was presented by Carlo-Stella et al.1 Findings as part of the larger cohort from the same trial that included fixed and step-up dosing (SUD), were also published recently in the Journal of Clinical Oncology.2 The fixed dose cohort demonstrated durable complete response and manageable safety profile in patients with R/R NHL.2 The updated results from the SUD cohort are summarized below.
This was a phase I dose-escalation trial, with SUD of glofitamab in patients with heavily pre-treated R/R NHL. Eligible patients were ≥18 years, had ≥1 prior lymphoma treatment and ≥1 measurable target lesion (>1/5 cm), and had an Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
A total of 52 patients received glofitamab SUD: 17 patients received 2.5/10/16 mg; and 35 patients received 2.5/10/30 mg glofitamab SUD. The SUD schedule was as shown in Figure 1. After Cycle 1 SUD, glofitamab was given every 3 weeks for a fixed duration of treatment up to 12 cycles.
Figure 1. Step-up dosing schedule*
C, cycle; D, day; Gpt, glofitamab fixed dosing with obinutuzumab pre-treatment.
*Adapted from Carlo-Stella et al1 and Hutchings et al.2
The median age of patients in the SUD cohort was 68 years (44−85) and patients had received a median of three prior lines of therapy (range, 1−12). Fifty-four percent of patients had aggressive non-Hodgkin lymphoma (aNHL), and 46% had indolent non-Hodgkin lymphoma (iNHL) (see Table 1).
Table 1. Baseline characteristics*
Characteristic |
2.5/10/16 mg and 2.5/10/30 mg cohorts (n = 52) |
---|---|
Prior therapy, % |
|
Chemotherapy and anti-CD20 monoclonal antibody |
100 |
Autologous stem-cell transplant |
21 |
PI3Ki |
10 |
CAR-T |
6 |
Cancer immunotherapy |
2 |
Refractory status, % |
|
Refractory to any prior therapy |
85 |
Refractory to most recent therapy line |
77 |
Refractory to any prior anti-CD20 |
73 |
Aggressive NHL, % |
54 |
DLBCL |
19 |
Transformed FL |
12 |
Ritcher transformation |
10 |
MCL |
10 |
High-grade B-cell lymphoma |
2 |
FL Grade 3b |
2 |
Indolent NHL, % |
46 |
FL Grade 1−3a |
46 |
CAR-T, chimeric antigen receptor T cell; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; NHL, non-Hodgkin lymphoma; PI3Ki, phosphoinositide 3-kinase inhibitor. |
Data presented from cutoff date of December 01, 2020.
Table 2. Response rates*
Response, % |
All patients |
2.5/10/16 mg cohort |
2.5/10/30 mg cohort |
---|---|---|---|
Aggressive NHL |
n = 28 |
n = 14 |
n = 14 |
CMR |
57 |
43 |
71 |
PMR |
7 |
7 |
7 |
ORR (CMR + PMR) |
64 |
50 |
78 |
Indolent NHL |
n = 24 |
n = 3 |
n = 21 |
CMR |
71 |
67 |
71 |
PMR |
8 |
33 |
5 |
ORR (CMR + PMR) |
79 |
100 |
76 |
CMR, complete metabolic response; PMR, partial metabolic response; ORR, overall response rate. |
Figure 1. CRS by dose and cycle*
CRS, cytokine release syndrome; C, cycle; D, day.
*Adapted from Carlo-Stella et al.1
†Multiple occurrences of CRS are counted to the highest grade.
Table 3. Adverse events*
AE, % |
All patients |
---|---|
Any AEs |
98 |
Treatment-related |
90 |
Serious AEs |
62 |
Treatment-related |
56 |
Grade 3−4 AEs |
60 |
Treatment-related |
40 |
Grade 5 AEs |
0 |
AEs leading to treatment discontinuation |
4 |
Treatment-related† |
4 |
AE, adverse event. |
The updated analysis showed that SUD of glofitamab had early, high, and durable response rates in patients with aNHL and iNHL who were refractory to multiple lines of therapy. Durability of responses was enhanced after completion of the fixed treatment period. The safety profile of SUD of glofitamab was manageable with mostly low-grade AEs confined to either Cycle 1 or 2.
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