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J. Duell et al.
Table 3. Treatment-emergent adverse events occurring in ≥10% of patients, or grade 3-5 treatment-emergent adverse events in >1 patient, reported at the updated L-MIND analysis.
Table 4. Summary of hematologic and non-hematologic treatment- emergent adverse events (any grade) by patient-years of exposure to tafasitamab.
Overall‡
Any TEAE, events/PYE 13.95
Hematologic, events/PYE* Neutropenia 1.73 Anemia 0.58 Thrombocytopenia 0.55 Leukopenia 0.44 Lymphopenia 0.13 Febrile neutropenia 0.06
Non-hematologic, events/PYE† Diarrhea 0.51 Pyrexia 0.31 Asthenia 0.30 Peripheral edema 0.29 Cough 0.24 Hypokalemia 0.23 Fatigue 0.19 Nausea 0.18 Hypomagnesemia 0.18 Constipation 0.17 Bronchitis 0.17 Decreased appetite 0.16 Respiratory tract infection 0.15 Hyperglycemia 0.15
All grades (≥10%) n (%)
41 (50.6) 30 (37.0) 25 (30.9) 12 (14.8) 10 (12.3) 6 (7.4)
29 (35.8) 20 (24.7) 22 (27.2) 19 (23.5) 19 (23.5) 18 (22.2) 16 (19.8) 15 (18.5) 14 (17.3) 14 (17.3) 12 (14.8) 12 (14.8) 13 (16.0) 12 (14.8) 10 (12.3) 10 (12.3) 10 (12.3) 9 (11.1) 9 (11.1) 8 (9.9)
7 (8.6)
Grade ≥3
(>1 patient) n (%)
40 (49.4) 6 (7.4) 14 (17.3) 9 (11.1) 10 (12.3) 3 (3.7)
1 (1.2) 2 (2.5) 1 (1.2) 0
1 (1.2) 0
2 (2.5) 5 (6.2) 2 (2.5) 0
0
0
1 (1.2) 0
8 (9.9) 2 (2.5) 1 (1.2) 0
0
2 (2.5) 3 (3.7)
N=81 Tafasitamab
Hematologic events Neutropenia Anemia Thrombocytopenia Leukopenia
Febrile neutropenia Lymphopenia
Non-hematologic events Diarrhea
Asthenia
Cough
Peripheral edema Pyrexia
Decreased appetite Back pain Hypokalemia Fatigue Constipation Muscle spasms Nausea
Bronchitis
Vomiting
All infective pneumonia*
All urinary tract infection* Dyspnea
C-reactive protein increased Respiratory tract infection Upper respiratory tract infection Hypertension
Extended plus § tafasitamab ¶
lenalidomide monotherapy
25.77 6.64
3.79 0.48 1.16 0.22 1.39 0.06 0.91 0.14 0.30 0.04 0.16 0
0.89 0.28 0.48 0.18 0.52 0.17 0.64 0.08 0.39 0.17 0.52 0.04 0.39 0.08 0.43 0.03 0.27 0.10 0.36 0.06 0.27 0.11 0.32 0.06 0.14 0.15 0.09 0.19
*Defined by customized Medical Dictionary for Regulatory Activities (MedDRA) query.
There were no cases of grade ≥3 infusion-related reac- tions, tumor lysis syndrome (of any grade), or cytokine release syndrome (of any grade) during the study.
In total, 14 patients (17.3%) received blood transfusions during the study, and 37 patients (45.7%) received granu- locyte colony-stimulating factor.
The median duration of common adverse events (all grades) was longest for opportunistic infections12 (20 days; 1 event each of progressive multifocal leukoen- cephalopathy, grade 5; hepatitis B reactivation, grade 2; Clostridium difficile colitis, grade 2; and skin candida, grade 1; 7 events of herpes viral infection, grade 1-4, including 1 event of grade 4 disseminated varicella zoster virus infec- tion in blood, gut, lungs and liver), followed by pneumo- nia and fatigue or asthenia (18 and 15 days, respectively) and shortest for nausea and vomiting (2 days).
Discussion
The primary analysis of the L-MIND study, at a median follow-up of 13.2 months, showed that combination ther- apy with tafasitamab and lenalidomide resulted in a promising response, including durable CR in a significant proportion of patients, and was well tolerated in trans- plant-ineligible patients with R/R DLBCL.8 With follow- up of at least 35 months, these long-term data confirm and extend the results of the primary analysis and provide more information on the consolidation tafasitamab
Treatment-emergent adverse events (TEAE) were defined as any adverse event report- ed in the following time interval (including the lower and upper limits): date of first administration of study treatment; date of last administration of study treatment + 30 days, or if they were considered to be related to the study drug. The Medical Dictionary for Regulatory Activities (MedDRA) version 21.0 coding dictionary was used. *Threshold for hematologic TEAE: ≥0.05 events per patient-years of exposure (PYE). †Threshold for non-hematologic TEAE: ≥0.15 events per PYE. ‡PYE was defined as the sum of duration of exposure for all patients, where duration of exposure was calculated as [(date of last dose of tafasitamab) – (date of first dose of tafasitamab) + 1]/365.25. §PYE was defined as the sum of duration of exposure for all patients, where duration of exposure was calculated as [(earliest date either study drug was discontinued) – (earliest date of administration of both study drugs) + 1]/365.25. Adverse event counts were for the combination treatment (tafasitamab + lenalido- mide) period only. ¶PYE was defined as the sum of duration of exposure for all patients, where duration of exposure was calculated as [(discontinuation date of taf- asitamab) – (earliest date of tafasitamab infusion after lenalidomide discontinuation) + 1]/365.25.Adverse event counts were for the tafasitamab monotherapy period only.
monotherapy phase of the study, with an objective response rate of 57.5%. This regimen was granted accel- erated approval by the US Food and Drug Administration for patients with R/R DLBCL not eligible for ASCT, based on a high response rate to therapy and prolonged DoR.13
This long-term follow-up analysis shows clinically sig- nificant durable responses for combination therapy fol- lowed by tafasitamab monotherapy. The median DoR was nearly 44 months with a median OS of 33.5 months; neither the median DoR nor the median OS was reached in patients with a CR, with 80.1% and 81.3% of patients with a CR in response or alive at 36 months, respectively (Figure 2A, C). The median PFS was notable in patients who received tafasitamab plus lenalidomide as second- line therapy compared with those who received the com- bination third-line or later (23.5 months vs. 7.6 months [n=40, both groups]). The corresponding median OS were 45.7 months vs. 15.5 months, suggesting that patients derive more benefit from this regimen when it is given in an earlier treatment setting.
Good response rates were also achieved with combina-
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haematologica | 2021; 106(9)