Page 342 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
emia; severely compromised hematologic function; and inadequate liver function or estimated glomerular filtration rate < 40 mL/min/1.73 m2 (those with renal dysfunction due to renal involvement could be included). All patients gave written informed consent prior to inclusion in this study, which was approved by the Institutional Ethics Committee of Peking Union Medical College Hospital (HS-2414) on June 23, 2020. Hematologic and organ responses were defined according to the current validated criteria.9-12 Patients who died before response assessment and did not have a post-baseline assessment were categorized under the no-response group. All analyses were performed based on the intention-to-treat principle.
From May 2021 to March 2022, 40 patients were included (Online Supplementary Figure S1). Baseline demographic and clinical characteristics are displayed in Table 1. One patient whose cardiac troponin-I was 0.07 μg/L was categorized as stage III since cardiac troponin-T was higher than 0.035 μg/L. The hematologic responses are presented in Table 2. The percentage of patients who had a hematologic VGPR or better at 3 months after treatment initiation was 67.5% (95% confidence interval [CI]: 52.3-82.7), including 47.5% (95% CI: 31.3-63.7) with CR and 20.0% (95% CI: 7.0-33.0) with VGPR, and the overall response rate was 82.5% (95% CI: 70.2-94.8). Considering the best hematologic response at any time point, the intention-to-treat estimate of the CR rate was 57.5%. Twenty-eight (70.0%) patients achieved difference between involved and uninvolved free light chain (dFLC) <10 mg/L or involved free light chain ≤20 mg/L. One patient experienced
hematologic progression and discontinued treatment after eight cycles. The median time to first hematologic response was 7 days (range, 7-28 days). The median time to hemato- logic CR was 60 days (range, 7-200 days).
A summary of the cardiac, renal and hepatic response as- sessments is shown in Online Supplementary Table S1. The percentage who had a cardiac response at 6 months was 47.5%, including 2.5% CR, 25.0% VGPR and 20.0% partial response. Cardiac progression at 6 months was observed in four (10.0%) patients. The median time to first cardiac response was 3 months (range, 1-11 months). The percent- ages of patients who had a renal response and a hepatic response were 41.7% and 20.0%. The median follow-up duration was 24.0 months. As of the last follow-up, eight patients had discontinued treatment due to cardiac sudden death, and two patients had died due to cardiac sudden death several months after withdrawal. Two patients died because of heart failure exacerbation from infection. The early mortality rates (within 1 month and 3 months from treatment initiation) were 15.0% and 17.5%, respectively. The 2-year OS estimate was 69.8% (95% CI: 53.0-81.6). Treatment-related adverse events (TRAE) are listed in On- line Supplementary Table S2. Grade ≥3 TRAE occurred in 16 (40.0%) patients. The most common grade 3 TRAE were diarrhea (10.0%). Grade 4 diarrhea was noted in one patient and improved after symptomatic treatment. Grade 3 or higher pulmonary infection were noted in three patients, including bacterial pneumonia in two patients and COVID-19 pneumonia in one patient. Grade 5 bacterial pneumonia
Table 2. Summary of overall confirmed hematologic responses (N=40).
All patients
3 months N (%)
Best hematologic response
N (%)
Day 8 N (%)
1 month N (%)
6 months N (%)
12 months N (%)
CR
19 (47.5)
23 (57.5)
2 (5.0)
9 (22.5)
20 (50.0)
21 (52.5)
VGPR
8 (20.0)
8 (20.0)
9 (22.5)
15 (37.5)
5 (12.5)
4 (10.0)
CR+VGPR
27 (67.5)
31 (77.5)
11 (27.5)
24 (60.0)
25 (62.5)
25 (62.5)
PR
6 (15.0)
6 (15.0)
15 (37.5)
10 (25.0)
3 (7.5)
2 (5.0)
ORR
33 (82.5)
37 (92.5)
26 (65.0)
34 (85.0)
28 (70.0)
27 (67.5)
Mayo stage IIIA CR
VGPR CR+VGPR PR
ORR
8 (40.0)
5 (25.0) 13 (65.0) 6 (30.0) 19 (95.0)
10 (50.0) 4 (20.0) 14 (70.0) 5 (25.0) 19 (95.0)
1 (5.0) 3 (15.0) 4 (20.0) 9 (45.0) 13 (65.0)
4 (20.0)
7 (35.0) 11 (55.0) 8 (40.0) 19 (95.0)
9 (45.0)
3 (15.0) 12 (60.0) 3 (15.0) 15 (75.0)
9 (45.0)
3 (15.0) 12 (60.0) 2 (10.0) 14 (70.0)
Mayo stage IIIB CR
VGPR CR+VGPR PR
ORR
11 (55.0) 3 (15.0) 14 (70.0) 0 (0.0) 14 (70.0)
13 (65.0) 4 (20.0) 17 (85.0) 1 (5.0) 18 (90.0)
1 (5.0) 6 (30.0) 7 (35.0) 6 (30.0) 13 (65.0)
5 (25.0)
8 (40.0) 13 (65.0) 2 (10.0) 15 (75.0)
11 (55.0) 2 (10.0) 13 (65.0) 0 (0.0) 13 (65.0)
12 (60.0) 1 (5.0) 13 (65.0) 0 (0.0) 13 (65.0)
CR: complete response; ORR: overall response rate; PR: partial response; VGPR: very good partial response.
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