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Long-term outcomes with tafasitamab in R/R DLBCL
Table 2. Efficacy outcomes in the primary and follow-up analyses. Tafasitamab plus lenalidomide (N=80)‡
Clinically relevant subgroups (follow-up analysis)
Best objective response, n (%) Complete response
Partial response
Stable disease
Progressive disease Not evaluable*
ORR (CR + PR), n (%) [95% CI]†
Median DoR (IRC), months (95% CI) Median PFS (IRC), months (95% CI) Median OS, months (95% CI)
Primary analysis (data cut-off: Nov 30, 2018)8
34 (42.5) 14 (17.5) 11 (13.8) 13 (16.3) 8 (10.0)
48 (60.0) [48.4-70.9]
21.7 (21.7-NR) 12.1 (5.7-NR) NR (18.3-NR)
Follow-up analysis (data cut-off: Oct 30, 2020)
32 (40.0) 14 (17.5) 13 (16.3) 13 (16.3) 8 (10.0)
46 (57.5) [45.9-68.5]
43.9 (26.1-NR) 11.6 (6.3-45.7) 33.5 (18.3-NR)
Primary refractory disease (n=15)
5 (33.3) 3 (20.0) 2 (13.3) 3 (20.0) 2 (13.3)
8 (53.3) [26.6-78.7]
NR (1.8-NR) 5.3 (0.9-NR) 13.8 (1.3-NR)
Rituximab-refractory disease (n=33)
13 (39.4) 5 (15.2) 4 (12.1) 7 (21.2) 4 (12.1)
18 (54.5) [36.4-71.9]
NR (5.8-NR) 7.6 (2.7-NR) 15.5 (8.6-NR)
Last-therapy- refractory (n=35)
14 (40.0) 7 (20.0) 3 (8.6) 7 (20.0) 4 (11.4)
21 (60.0) [42.1-76.1]
NR (5.8-NR) 7.6 (2.7-NR) 15.5 (8.6-NR)
*Non-evaluable patients had no valid post-baseline response assessments. †Using the two-sided 95% Clopper-Pearson exact method based on a binomial distribution. ‡One patient received tafasitamab only. ORR: objective response rate; CR: complete response; PR: partial response; 95% CI: 95% confidence interval; DoR: duration of response; IRC: independent review committee; PFS: progression-free survival; OS: overall survival; NR: not reached.
discontinuation of lenalidomide at any time [n=52]) was 13.9 months (range, 0.2-43.4), compared with a median of 4.1 months’ exposure to tafasitamab monotherapy in the primary analysis (range, 0.1-20.8 months; data cut-off November 30, 2018).8 However, with the exception of one patient with recurrence of a previously diagnosed marginal zone lymphoma that was documented as an adverse event (Figure 1), no patients discontinued the study due to adverse events during the tafasitamab extended monotherapy phase.
Overall, 64 (79.0%) patients required a temporary inter- ruption of tafasitamab, of which 73.4% cases were due to adverse events. During combination therapy, 43 (53.1%) patients required no dose reduction of lenalidomide from the starting dose of 25 mg. Lenalidomide interruptions were required by 28 (34.6%) patients, being due to adverse events in 89.3% of cases, and 37 patients (45.7%) required a lenalidomide dose reduction. The most fre- quent treatment-emergent adverse event (TEAE) leading to treatment interruption for tafasitamab (± lenalidomide) and lenalidomide (± tafasitamab) was neutropenia (28 [34.6%] patients and 24 [29.6%] patients, respectively). During the extended tafasitamab monotherapy phase, 21 (52.5%) patients had an interruption of tafasitamab treat- ment due to at least one TEAE, the most common reasons being neutropenia or leukopenia (9 patients) and respira- tory tract infections (6 patients).
At the current analysis, 42 patients (51.9%) had died. There were eight deaths (9.9%) on treatment (5 related to PD, plus 1 stroke, 1 sudden death and 1 respiratory fail- ure), and 34 deaths (42.0%) after treatment (26 related to PD, plus 1 intracerebral hemorrhage, 1 pulmonary edema due to heart failure, 1 pneumonia, 1 end-stage marrow failure, 1 progressive multifocal leukoencephalopathy, 1 congestive heart failure and 1 acute myeloid leukemia considered by the investigator to be secondary to past chemotherapy, and 1 unknown cause).
At a median follow-up for OS of 42.7 months, com- pared with 19.6 months at the primary analysis (an addi- tional follow-up duration of 23.1 months), TEAE were consistent in incidence and severity with the those of the primary analysis (Table 3), with the most common TEAE (all grades) at extended follow-up remaining neutropenia (51%) and anemia (37%). The adverse event burden,
expressed in terms of number of adverse events per patient-year of exposure to study medication, decreased greatly during the tafasitamab monotherapy phase com- pared with that during the combination therapy phase (Table 4). Consistent with the safety profile of tafasitam- ab monotherapy in other studies,10,11 the most common adverse events during the monotherapy phase were neu- tropenia, cough, diarrhea, anemia, nasopharyngitis, and pyrexia, and the majority of adverse events were of grade 1 or 2. Similar to the primary analysis, the most common grade ≥3 TEAE were neutropenia (49%), thrombocytope- nia (17%) and febrile neutropenia (12%).
Treatment-emergent serious adverse events (SAE) were reported in 43 patients (53.1%). The most common SAE were pneumonia (7 patients [8.6%]), febrile neutropenia (5 patients [6.2%]), pulmonary embolism (3 patients [3.7%]), bronchitis, lower respiratory tract infection, atri- al fibrillation and congestive cardiac failure (all 2 patients [2.5%]). Of these, pneumonia and lower respiratory tract infection had been reported in an additional two and one patients, respectively, compared with the primary analy- sis, while the rest remained unchanged. Overall, ten patients (12.3%) experienced febrile neutropenia (grade 3 or 4). Five of these patients also developed infections whose timing was associated with febrile neutropenia (urinary tract infection [grade 3 adverse event]; sepsis and urinary tract infection [both grade 4 SAE]; Enterobacter bacteremia [grade 3 SAE]; staphylococcal skin infection [grade 2 adverse event]; rhinitis [grade 1 adverse event] and respiratory syncytial virus infection [grade 3 SAE]), and all recovered within 3-24 days; the other five patients developed no infections at all or their timing was not associated with febrile neutropenia.
Between the primary analysis and this update, there were few new adverse events reported related to infec- tion and rash (Online Supplementary Table S2). This obser- vation is consistent with the low incidence of these events associated with tafasitamab monotherapy.
Eleven patients (13.6%) experienced 13 TEAE of special interest, including tumor flare (3 events in 3 patients [3.7%]), allergic dermatitis (3 events in 3 patients [3.7%]), basal cell carcinoma (4 events in 2 patients [2.5%]), myelodysplastic conditions (2 events in 2 patients [2.5%]), and Bowen disease (1 event in 1 patient [1.2%]).
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