Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy

Figures & data

Figure 1. Patient attrition from FH database. 3L+: third or subsequent line of systemic therapy; ECOG: Eastern Cooperative Oncology Group; FH: Flatiron Health; FL: follicular lymphoma. ^aPatients were probabilistically sampled from an overall cohort of N = 207,263 patients with an ICD code for FL in the Flatiron Health network. ^bDefined as a regimen including at least one agent recommended by the NCCN Guidelines v4.2022 for the treatment of FL. ^cOf 158 patients, all had progression and/or survival data available but 33 did not have response data available in their index line of systemic therapy, resulting in N = 125 response-evaluable patients and N = 158 time-to-event evaluable patients.

Table 1. Baseline demographic and clinical characteristics of patients from the mosunetuzumab and RWD cohorts, before (pre) and after (post) PSM weighting.

	Mosunetuzumab, N = 90^a	Weighted RWD		SMD^a
		Pre, N = 158^b	Post, N = 88^b	Pre	Post
Prognostic factors included in the PSM
Median age at index line, years (IQR)	60 (53, 66)	68 (57, 75)	59 (53, 69)	0.44	0.01
POD24, n (%)	47 (52)	74 (47)	42 (48)	0.11	0.08
Refractory to last prior line, n (%)	62 (69)	102 (65)	59 (67)	0.09	0.04
Double refractory, n (%)	48 (53)	121 (77)	48 (55)	0.50	0.03
Number of prior lines, n (%)
2	34 (38)	111 (70)	33 (37)	0.75	0.07
3	28 (31)	34 (22)	30 (34)
4+	28 (31)	13 (8.2)	25 (29)
Factors not included in the PSM
Sex, n (%)
Female	35 (39)	71 (45)	–	–	–
Male	55 (61)	87 (55)	–	–	–
Race, n (%)
White	74 (82)	110 (70)	–	–	–
Non-White	13 (14)	8 (5.1)	–	–	–
Other/Unknown	3 (3.3)	40 (25)	–	–	–
Median time from initial FL diagnosis to frontline, months (IQR)	1 (0, 7)	1 (0, 3)	–	–	–
Median time from initial FL diagnosis to index, months (IQR)	81 (51, 129)	44 (22, 64)	–	–	–
Index regimen, n (%)
Anti-CD20 + chemo^c	–	58 (37)	–	–	–
Anti-CD20 + lenalidomide	–	26 (16)	–	–	–
Anti-CD20 monotherapy	–	23 (15)	–	–	–
PI3K inhibitors	–	26 (16)	–	–	–
Other^d,e	–	25 (16)	–	–	–
Mosunetuzumab	90 (100)	–	–	–	–

FL: follicular lymphoma; IQR: interquartile range; M: mosunetuzumab; PI3K: phosphoinositide 3-kinase; POD24: progression of disease in 24 months; PSM: propensity score model; RWD: real-world data; SMD: standardized mean difference.

^aBalance between the RWD and M cohorts was considered achieved if the SMD of at least half of the prognostic variables in the PSM was <0.25. ^bA subset of 125 patients were included in the response-evaluable cohort. ^cOne patient received a stem cell transplant as part of the ‘anti-CD20 + chemo’ index regimen. ^dOne patient received a stem cell transplant as part of the ‘other’ index regimen. ^eDefined as a regimen including at least one agent recommended by the NCCN Guidelines v4.2022 for the treatment of FL.

Figure 2. Weighted response rates in mosunetuzumab single-arm trial and real-world data cohorts. Bar plots show weighted complete and overall response rates by study cohort. Numbers above each bar correspond to the percentage of participants responding with 95% confidence intervals (also represented by the error bars).

Figure 3. Forest plots of sensitivity analyses for (A) overall response rate, (B) complete response rate, (C) progression-free survival, and (D) overall survival. Each Forest plot shows the weighted association between study cohort and each outcome of interest, adjusting for months from diagnosis to index line initiation. Each row in the Forest plot corresponds to a separate sensitivity analysis conducted. The blue square represents the estimate (HR or or) while the horizontal line represents the 95% confidence interval. Upper or lower confidence limits that are outside the plot range are depicted with an arrow.

CI: confidence interval; HR: hazard ratio; I/E: inclusion/exclusion criteria; LoT: line of therapy; M: mosunetuzumab; OR: odds ratio; SS: sample size.

Table 2. Comparison of clinical outcomes between mosunetuzumab and RWD cohorts.

Endpoint	Treatment arm		Mosunetuzumab vs RWD (reference)
	Mosunetuzumab	RWD (after weighting)
Response rate	N = 90	N = 87^a	Odds ratio (95% CI)^b	E-value (CI)
	Proportion responding (95% CI)
Primary: ORR	0.80 (0.72, 0.88)	0.75 (0.63, 0.86)	1.23 (0.52, 2.93)	1.46 (1.00)
Secondary: CR rate	0.60 (0.50, 0.70)	0.33 (0.19, 0.47)	3.18 (1.41, 7.17)	2.97 (1.66)
Time-to-event	N = 90	N = 88^c	Hazard ratio (95% CI)^d	E-value (CI)
	Median time-to-event (months, 95% CI)
Secondary: PFS	17.9 (10.1, NR)	10.1 (6.54, 22.8)	0.82 (0.53, 1.27)	1.56 (1.00)
Secondary: OS	NR	NR	0.43 (0.19, 0.94)	4.14 (1.34)
12-month OS	0.93 (0.88, 0.98)	0.76 (0.64, 0.88)	–	–
Exploratory: TTNT	NR (16.2, NR)	19.4 (8.98, 22.6)	0.77 (0.47, 1.26)	1.68 (1.00)

CI: confidence interval; CR: complete response; NR: not reached; ORR: overall response rate; OS: overall survival; PFS: progression-free survival; RWD: real-world data; TTNT: time-to-next-treatment.

^aSample size in the response-evaluable cohort after weighting (i.e. the sum of weights). The effective sample size was 47. ^bWeighted logistic regression model as a function of study cohort and months from diagnosis to index line initiation. 95% CIs constructed using a robust estimator for the standard error. ^cSample size in the time-to-event-evaluable cohort after weighting (i.e. the sum of weights). The effective sample size was 47. ^dWeighted Cox proportional hazards model as a function of study cohort and months from diagnosis to index line initiation. 95% CIs constructed using a robust estimator for the standard error.

Figure 4. Weighted Kaplan-Meier plots comparing mosunetuzumab single-arm trial to RWD for (A) overall survival, (B) progression-free survival, and (C) time-to-next treatment. Solid lines represent Kaplan-Meier survival probabilities; shading represents 95% confidence intervals. PFS: progression-free survival; RWD: real-world data; TTNT: time-to-next treatment.

Data availability statement

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