Characteristics of the patients in the test cohort
The test cohort included 62 patients (median age 63 years, sex ratio M/F = 1,9). Anti-HLA antibodies were found in 23% (14/62) of the patients. Among the 14 patients with positive anti-HLA antibodies, 9 had a second sample available, and anti-HLA antibodies disappeared in 6 of them after daratumumab treatment (Fig. 1). All patients received treatment including PI and IMiD and half received an alkylating agent (Table 1). Most of the patients in this cohort had a previous history of transfusion (7/9).
Evolution of anti-HLA antibodies in the test cohort
In this cohort, the median time between the first and the second anti-HLA antibody sample was 290 days [40-1384] and in the daratumumab group, the median time was 251 days. 3 patients received daratumumab as monotherapy, and 5 in combination with PI, IMiD, or Alkylating agent. In patients treated with daratumumab, anti-HLA antibodies disappeared in 75% of cases (6/8). Considering both decrease and loss of anti-HLA antibodies, the rate reached 88% (7/8).
Characteristics of patients in the validation cohort
The validation cohort included 120 patients. Anti-HLA antibodies were detected in 70 patients (58%). A second sample was available for 42 patients and 2 patients were excluded because the interval between the two samples was less than 5 days. 21 patients showed positive anti-HLA antibodies on their second sample (Fig. 1).
We further studied 40 patients (37 MM and 3 AL) who received a median of 2 lines of treatment [0–4]. 11 patients were not yet treated at the time of the first sample. Of the 29 patients under treatment, 26 (90%) received a PI, 22 (76%) patients received an IMiD, 11 (40%) received an alkylating agent, and 15 patients (52%) underwent high dose chemotherapy followed by an autologous stem cell transplant (Table 1).
Half of the patients received a transfusion (red blood cells, platelets and plasma) (20/40). Among the 24 males in this cohort, 13 (33%) did not have any prior history of transfusion.
Evolution of anti-HLA antibodies in the validation cohort
In the validation cohort, the median time between the two serum samples was 92 days [21–779 days] and in the daratumumab group, the median time was 63 days. 19 out of 40 patients received treatment including daratumumab, in monotherapy (n = 2), and in combination with a PI, IMiD, or alkylating agent (n = 17). 21 patients received only treatment a PI, IMiD, or alkylating agent. The rate of anti-HLA antibody loss was similar in patients treated with daratumumab (47%) or without (48%).
A subgroup of 16 out of 19 (84%) patients treated with daratumumab had complete loss or decreased anti-HLA antibody levels. In the subgroup treated without daratumumab, loss or decrease of anti-HLA antibodies was observed in 81% (17/21).
Evolution of anti-HLA antibodies in the whole cohort
To analyze the effect of daratumumab on a larger number of patients, the two cohorts were combined. Therefore, we considered an overall cohort of 49 patients, including 27 patients treated with daratumumab and 22 patients without. Among the 25 patients with negative anti-HLA antibody levels, 15 patients (60%) received daratumumab versus 10 patients (40%) without daratumumab, p = 0.57.
85% (23/27) of patients treated with daratumumab, either reduced or completely lost anti-HLA antibodies, as compared to 77% (17/22) for patients treated without daratumumab (Fig. 2) (p = 0.83).
In the 25 patients achieving anti-HLA antibodies level complete loss, the median treatment exposure was shorter in the presence of daratumumab than with other therapies: 112 days [27–516] versus 169 days [31–779], respectively (Fig. 2).
Impact of daratumumab as monotherapy or in combination
Five patients were treated with daratumumab in monotherapy and 22 patients received daratumumab in combination with PI or IMiD: 2 out of 5 patients had negative anti-HLA antibodies levels versus 13 out of 22 patients respectively (p = 0.6). In addition, 4 out of 5 (80%) patients treated with daratumumab alone decreased or lost anti-HLA antibody level as compared to 19 out of 22 (86%) other patients, p = 1.0. Hence, daratumumab alone or in combination should have a similar impact on the anti-HLA antibody level.