PB2139 IMPACT OF OVERWEIGHT IN TREATMENT WITH DARATUMUMAB IN MULTIPLE MYELOMA PATIENTS
Authors: Roque A. , Afonso M. C. , Rito L. , Pereira M. , Araújo L. F. , Geraldes C. , Ribeiro M. L. 
Published: June 2019

Background:

Daratumumab (Dara) is a monoclonal antibody (mAb) directed against CD38, that is extensively expressed on plasma cells, but also in adipocytes, being an important determinant for adipose tissue differentiation. Some studies revealed lower serum levels of mAb in overweight (OW) pts, with decreased efficacy. Besides that, the best method to establish mAb dosage is debated–actual body weight (ABW), body surface area (BSA) or fixed dosing (FD). Because there is a probability of Dara‐adipocyte interaction, and being Dara dosage calculated according to ABW, with higher adiposity and consequent increasing of CD38 expression, there is a possibility that Dara efficacy can be decreased, or toxicity increased in OW patients (pts).

Aims:

To evaluate OW impact in adverse effects and outcome of pts treated with Dara.

Methods

Retrospective analysis of MM pts treated with Dara from 2017 to 2018. Disease characteristics, adverse events and outcome were evaluated and correlated with biometrical data. Dara was administered in a dosage of 16 mg/kg according different protocols. OW was defined as a body mass index (BMI) ≥25 kg/m2. Toxicities were graded according to CTCAE v4.03. Disease response was defined according to IMWG criteria.

Results:

During this period, 23 pts started treatment with Dara, median age 61 years (36‐76), 52.2% of male. The most frequent subtype was IgGκ (47.8%), and 34.8% were ISS III. At diagnosis, 87.0% had bone and 13.0% extramedullary disease. From 11 pts with available cytogenetics, 54.5% presented high‐risk cytogenetic abnormalities.

The median time between diagnosis and Dara was 67 months (6‐ 204), for a median number of previous therapeutic lines of 2 (1‐5) (≥4 in 47.8%). All pts had received bortezomib, 56.5% an immunomodulator and 82.6% autologous hematopoietic stem cell transplantation. Dara was used in monotherapy in 13.0%, associated with pomalidomide/dexamethasone in 13.0%, and with lenalidomide/dexamethasone in 73.9%.

At first Dara infusion, 39.1% pts (n = 9) had grade≥2 adverse events. During treatment, 87.0% pts developed at least one grade≥2 cytopenia ‐ grade≥3 anaemia in 2, neutropenia in 9, thrombocytopenia in 5. Ten pts (43.5%) developed infection, mainly respiratory, and 3 pts had venous thromboembolism, probably related with lenalidomide. The median number of admissions was 1 (1‐3), with 48% needing for treatment delay. After 4 and 12 Dara infusions, 73.3 and 82.4% of pts had reached partial response (PR) or higher, respectively. At time of last follow up, 39.1% had stopped Dara–3 due to death (2 with progressive disease [PD]), 3 due to PD and 3 for aHSCT. Median overall survival (OS) after Dara was 16.1 months.

Considering BMI, 9 pts (39.1%) were OW. There were no statistically significant differences between pts with and without OW considering clinical characteristics at MM diagnosis and at the time of starting Dara, previous treatment, adverse events and response to Dara (p = NS). There was no difference in OS between non‐OW and OW pts (16.1 months vs NR; p = 0.061).

Summary/Conclusion:

Because mAb are target‐specific drugs, their therapeutic range is large, with a limited contribute of weight in pharmacokinetics. Contrary to our hypothesis, that Dara interaction with adipocytes can affect its efficacy and safety profile, in this cohort there were no differences in response and adverse events between OW and non‐OW pts. However, controversial remains active concerning the best approach to calculate Dara dosage–ABW, BSA, FD–considering efficacy, toxicity, and cost‐effectiveness.