Daratumumab In Patients Research Articles

First-Line Use of Daratumumab in Patients with Multiple Myeloma Shows Delayed Neutrophil and Platelet Engraftment after Autologous Stem Cell Transplantation: Results from a Real-Life Single-Center Study.

This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m2. These patients were compared with a historical control group of 80 patients who received four cycles of VTd as induction therapy. The median days to reach neutrophil and platelet engraftment significantly differed between patients treated with D-VTd (11 and 13 days, respectively) and VTd (10 and 12 days). Univariate Cox analyses show that patients treated with D-VTd had a hazard ratio of neutrophil engraftment that was 42% significantly lower than those in the VTd arm (HR: 0.58, p = 0.002), and a multivariate model confirmed this result. Patients treated with D-VTd developed FN more frequently. Univariate and multivariate logistic regressions revealed an association between D-VTd and FN. Delayed engraftment did not correlate with more extended hospitalization. No patients died in the first six months after transplantation. Our real-life study showed that a four-drug induction therapy containing DARA does not impact transplant safety outcomes.

A Pilot Study of the CD38 Antagonist Daratumumab in Patients with Metastatic Renal Cell Carcinoma or Muscle-Invasive Bladder Cancer.

We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC). Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring design for toxicity was used for excessive toxicity. In both the MIBC (n = 8) and mRCC (n = 8) cohorts, no toxicity events were encountered. In the MIBC cohort, one patient experienced pathologic complete response rate. In the mRCC cohort, no objective responses were reported, and the median progression-free survival was 1.5 months (95% confidence interval, 1.1-1.8 months). Immune monitoring found significant reductions in NK cells in circulation in both cohorts after treatment. In the tissue analysis, IHC found evidence of diminished CD38 presence in mRCC with treatment, whereas the baseline levels in MIBC were low. Treatment with daratumumab was safe. No signal of efficacy was detected in mRCC, and conclusions on the activity in MIBC were limited. Evidence of daratumumab targeting CD38 was detected in circulating immune cells and within the tumor microenvironment of mRCC and MIBC. In this prospective clinical trial of daratumumab, treatment in patients with MIBC and mRCC was safe. Limited efficacy was observed. Treatment with daratumumab resulted in CD38-expressing immune cell subsets to be targeted both in circulation and within the tumor microenvironment.

Mechanisms of resistance to daratumumab in patients with multiple myeloma.

Multiple myeloma (MM) is an incurable cancer in the bone marrow. The treatment of MM has developed significantly during the last 20 years, which has resulted in increased survival. Daratumumab is the first CD38 antibody approved for the treatment of MM. It has improved the treatment of MM even further. This is an evaluation of the modes of action of daratumumab and a description of the development of resistance with a focus on inhibitory checkpoint receptors on CD8+ T-cells, complement activation and extracellular vesicles.

Efficacy of a Daltuzumab-containing Regimen in Patients with mSMART High-Risk Multiple Myeloma

To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score. Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed. The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections. Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

Identifying clinical response to daratumumab therapy in relapsed/refractory multiple myeloma using a patient-derived in vitro model.

Response to daratumumab in patients with relapsed/refractory multiple myeloma is heterogeneous, and a reliable biomarker of response is lacking. We aimed to develop a method that identifies response to daratumumab therapy. Patient-derived MM cells were collected before start of daratumumab treatment and were cultured in a hydrogel-based culture system. The extent of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro was associated with both clinical response and progression-free survival in corresponding patients. Together, our results demonstrate that in vitro sensitivity to daratumumab therapy in a hydrogel culture with primary MM cells might be used to identify patients most likely to benefit from treatment.

A Prospective Phase II Clinical Study of Low-Frequency Daratumumab for the Treatment of Systemic Light Chain Amyloidosis

Purpose: Systemic light chain (AL) amyloidosis is a disease caused by the misfolding of monoclonal immunoglobulins light chain to form amyloid, which is deposited in tissues and organs, resulting in structural destruction of tissues, organ dysfunction, and progressive progression. Daratumumab is a human CD38-targeting antibody that has been used for the treatment of patients with AL amyloidosis. This is a prospective, single-arm phase II clinical study designed to explore the efficacy and safety of low-frequency Daratumumab in patients with AL amyloidosis. Methods: A total of 47 patients are expected to be enrolled in this study. As of May. 01, 2023, a total of 38 patients with AL amyloidosis meeting the inclusion criteria were included. Low-frequency Daratumumab was administered at 16 mg/kg every two weeks for weeks 1-8 and every four weeks for weeks 9-24, either alone or in combination with bortezomib. The regimen may be discontinued after week 25, or Daratumumab monotherapy every eight weeks for up to two years for maintenance therapy. The efficacy of the previous treatment was assessed before each regimen of Daratumumab. Follow-up was performed every three months after treatment cessation until disease progression or death of the patient from any cause. Results: Of the included patients, 27 (71.1%) were male, with a median age of 64 years (59-71). The median number of involved organs was 2 (1-3), of which 27 (71.1%) had renal involvement, 34 (89.5%) cardiac involvement, and 6 (15.8%) hepatic involvement. 28 (73.7%) were newly diagnosed patients and 10 (26.3%) were recurrent and refractory patients. There were 25 (65.8%) Mayo 2004 stage III patients and 23 (60.6%) Mayo 2012 stage III/IV patients. The median number of treatment cycles was 5 (2-8). All patients (100%) achieved hematologic very good partial response or above (≥VGPR), of which 18 (48.6%) patients achieved hematologic complete response or above (≥CR). The median time to hematologic remission was 15.0 days (14.0-29.0 days) and the median time to hematologic CR was 92.5 days (28.0-119.3 days). 9 (40.9%) patients achieved renal remission, with a median response time of 41.0 days (29.0-87.0 days).11 (33.3%) patients achieved cardiac remission, with a median response time of 145.0 days (30.0-223.0 days). And 1 (16.7%) patient achieved hepatic remission. At a median follow-up of 11.8 months (9.8-13.7 months), median progression-free survival (PFS) and overall survival (OS) were not reached, with a 6-month PFS of 91.0% and a 6-month survival OS of 91.0%. In terms of safety, the most common adverse events were fatigue (22 cases, 57.9%), infection (18 cases, 47.4%), and fever (16 cases, 42.1%). 7 (18.4%) patients had Daratumumab-related infusion reactions. Conclusion: The results of this study showed that the low-frequency daratumumab regimen demonstrated good hematological and organ efficacy in the treatment of patients with AL amyloidosis. Patients had a high early survival rate and better safety profile.

Real-world Duration of Use and Dosing Frequency of Daratumumab in Patients With Multiple Myeloma in the United States

Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as a combination therapy for newly diagnosed multiple myeloma (MM) and as monotherapy and combination therapy for relapsed or refractory MM cases. We assessed the length of DARA use across lines of therapy and the probabilities of treatment discontinuation in patients with MM in the real-world. We used the deidentified Clinformatics Data Mart database from Optum to identify patients with MM (n=2124) who received DARA-containing treatment between November 1, 2015 and March 31, 2021 in the United States. Patients were excluded if they had received a stem cell transplant. The duration of DARA use was defined as the time interval between the first initiation and discontinuation of DARA as a time-to-event outcome using the Kaplan-Meier method. A gap of more than 60 days between 2 consequent DARA claim dates was defined as DARA discontinuation. The median duration of continuous DARA use was 16.6 months. By 24 months, 33.1% of patients remained on DARA treatment. In a subgroup analysis of patients with 12 months or more continuous insurance coverage (n=1246), the median length of DARA use was 24.7 months; by 24 months, 51.8% remained on DARA treatment. The dose adherence ratios (observed DARA doses relative to the label) were close to 1.0, particularly among patients with longer follow-up, indicating that real-world DARA dosing frequency was similar to that on the approved label. In summary, this real-world analysis reported that the median duration of continuous DARA use is 16.6 months, with high dosing adherence in patients who have MM.

P-050 GEN3014 (HexaBody-CD38) versus daratumumab in patients with relapsed/ refractory multiple myeloma: design of randomized head-to-head expansion cohort of phase 1/2 trial

P-050 GEN3014 (HexaBody-CD38) versus daratumumab in patients with relapsed/ refractory multiple myeloma: design of randomized head-to-head expansion cohort of phase 1/2 trial

Safety and feasibility of 120 min rapid infusion regimen of daratumumab in patients with multiple myeloma

Safety and feasibility of 120 min rapid infusion regimen of daratumumab in patients with multiple myeloma

A Phase II, Open-Label Study of an Accelerated Infusion Rate of Daratumumab in Patients With Relapsed and Refractory Multiple Myeloma.

Daratumumab is an anti-CD38 monoclonal antibody initially approved as a single agent for the treatment of relapsed and refractory multiple myeloma. The infusion-related reactions (IRRs) commonly seen with intravenous daratumumab have been managed by prolonging the first infusion, temporarily stopping/slowing the rate if reactions occur and using adequate pre- and post-infusion medications. Several retrospective studies have evaluated shorter infusions after ≥ 2 prior doses administered at the standard rates. Although the shorter infusions were well-tolerated, patients in these reports were given heterogeneous daratumumab regimens and had often already received multiple doses at the longer standard rates. CMRG-009 is a prospective study designed to demonstrate the safety of accelerated daratumumab infusions commencing with the second dose. After an initial dose on Cycle 1 Day consisting of 8 mg/kg over 4 hours, all subsequent doses were given over 90 minutes. No grade 3 IRRs were observed with the 90-minutes infusions. Both the safety profile and anti-myeloma effects were otherwise similar to those observed with other single agent daratumumab studies using longer infusion times. This is the first formal prospective trial using infusion times shorter than the standard schedule directly after an initial 4-hours dose. This rapid infusion protocol has resulted in more efficient resource utilization and has become the standard protocol for the use in all intravenous daratumumab regimens in Canada. This approach has been particularly helpful in shortening chair time during the COVID-19 pandemic and providing a useful alternative in jurisdictions without access to subcutaneous daratumumab.

A phase IIb study of selinexor in combination with carfilzomib, daratumumab, or pomalidomide in patients with multiple myeloma relapsing on current therapy.

e20042 Background: Selinexor is an oral, selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1), leading to retention of tumor suppressor proteins and apoptosis in malignant cells. Preclinical studies suggest synergistic activity when selinexor is combined with other treatments for MM. We hypothesize the addition of selinexor can recapture response to patients relapsing or refractory on carfilzomib (CFZ), pomalidomide (POM) or daratumumab (DARA)-based regimens. Methods: This is an ongoing phase IIb, open-label, multicenter study to evaluate the safety and efficacy of selinexor plus CFZ, POM, or DARA in patients with MM. Patients were enrolled to each arm only if their disease was refractory to the specific drug of interest (CFZ for Arm 1, POM for Arm 2, and DARA for Arm 3). Arm 1 (n=1) consists of selinexor 80 mg orally on D1, 8, 15; CFZ 56 mg/m2 IV on D1, 8, 15; and dexamethasone (DEX) on D1, 8, 15, 22. Arm 2 (n=7) consists of selinexor 60 mg orally on D1, 8, 15; POM 4 mg orally on D1-21; and DEX on D1, 8, 15, 22. Arm 3 (n=7) consists of selinexor 100 mg orally on D1, 8, 15, 22; DARA 16 mg/kg IV or 1,800 mg SQ on D1, 8, 15, 22 for C1-2; D1 and 15 for C3-6; D1 for ≥C7; and DEX on D1, 8, 15, 22. The primary endpoint is ORR and secondary endpoints include PFS, OS, MRD negativity and TEAEs. Results: At data cutoff (Feb 6 2023), 15 patients were enrolled with a median age of 64 years (range 60-83), 27% with ISS stage III MM, 73% with high-risk cytogenetics, 93% refractory to the last LOT, 47% triple refractory, and 33% quadruple refractory (Table). The ORR was 33% (4/12; 4 PR) and the CBR was 92% (11/12; 7 SD); 3 patients are pending. The most common grade 3-4 TEAEs (n=34) were neutropenia (32%), hypophosphatemia (9%), pneumonia (6%), hyperglycemia (6%), and fatigue (6%). Ten patients discontinued treatment due to PD (n=5), withdrawal of consent (n=2), or TEAEs (n=3; fall, diarrhea, and RSV pneumonia), of whom 1 patient died while hospitalized for diarrhea and weakness. Conclusions: Preliminary results show selinexor plus CFZ, POM, or DARA is safe and restores sensitivity to therapy in relapsed/refractory MM patients. In this population of heavily pretreated MM patients, the ORR (33%) and CBR (92%) observed are higher compared to those seen with single-agent selinexor (ORR 4% and CBR 21%) (Chen C et al, Blood 2018). Clinical trial information: NCT04661137 . [Table: see text]

Clinical Administration Characteristics of Subcutaneous and Intravenous Administration of Daratumumab in Patients With Multiple Myeloma at Mayo Clinic Infusion Centers.

Median duration of daratumumab (DARA) administration for treatment of multiple myeloma is 3-7 hours for the intravenous formulation (DARA IV) and 3-5 minutes for the subcutaneous formulation (DARA SC). Here, we describe clinical administration characteristics of DARA using a novel method for data extraction from electronic health records. Time-based measurements were extracted using a scheduling/pharmacy software program that tracked patient movement through appointments for patients initiating DARA in Mayo Clinic infusion centers from April 5, 2017, to October 14, 2021. Cohorts included patients who received DARA IV or DARA SC, or converted from DARA IV to DARA SC. The DARA SC cohort was further analyzed before (DARA SC initial) and after (DARA SC shortened) a reduction in the postadministration observation time mandated by the treatment plan. Events associated with administration-related reactions (ARRs) were also identified. Median total clinic times were 2.7-3.0 hours shorter for DARA SC versus DARA IV. Median clinic times were highest at dose 1 and decreased with subsequent doses. Median total chair times were 2.7-2.8 hours shorter for DARA SC versus DARA IV. Incidences of ARR-related events with DARA SC were low across doses. Reduced clinic times were observed with DARA SC, indicating that use of DARA SC as a treatment option results in time savings that may free clinic resources. Furthermore, novel methods of electronic health record data extraction can provide insights that may help inform clinic resource optimization.

SA58 Real-World Outcomes for the Treatment of Relapsed/Refractory Multiple Myeloma With Daratumumab: A Systematic Literature Review

To characterize real-world outcomes of daratumumab in patients with relapsed/refractory multiple myeloma (RRMM).

Real-World Outcome of Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma: A Multicenter Propensity Score Matched Case Series Study

Real-World Outcome of Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma: A Multicenter Propensity Score Matched Case Series Study

Elranatamab in Combination with Daratumumab for Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 3 Magnetismm-5 Study Safety Lead-in Cohort

Elranatamab in Combination with Daratumumab for Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 3 Magnetismm-5 Study Safety Lead-in Cohort

Efficacy and safety of daratumumab in patients with relapsed/refractory multiple myeloma

Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) μmol/L, which was significantly higher than that of low dosage group [66 (51, 76) μmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.

MM-315 Light-Chain Amyloidosis Patients Treated With Daratumumab: A Single-Center Experience

Light chain (AL) amyloidosis is an extreme form of systemic amyloidosis, causing organ dysfunction, mainly affecting the heart and kidneys. Daratumumab was the first monoclonal CD38 antibody approved for the treatment of AL amyloidosis. There are few real-world data about the use of daratumumab in patients with AL amyloidosis from Latin America. Describe the hematological and organ response in patients with AL amyloidosis treated with daratumumab. A retrospective cohort of patients with AL amyloidosis in a single center treated with daratumumab from January 2018 to April 2022. Daratumumab was administered intravenously with low-dose dexamethasone alone or in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD). Doses were adjusted to reduce toxicities. Twelve patients were included. The overall median age was 64 (IQR, 43-77) years old, eight (67%) were female. Five patients were newly diagnosed, while seven patients had relapsed or refractory disease. One patient died during the first cycle of daratumumab, and the remaining 11 patients completed a median of 11 (IQR, 2-30) cycles. Overall, ten (83%) patients presented a hematologic response, six (60%) presented a very good partial response or better after a median of 1.5 cycles of treatment. Median time-to-hematologic response was 1.5 months. Nine patients (75%) had cardiac involvement, three had IIIB and two patients had IIIC cardiac stage respectively. Four (44%) of evaluable patients achieved a cardiac response, with a median time to response of 8 months. Six patients (50%) had renal involvement, and two (33%) of evaluable patients achieved a renal response, with a median response time of 16 months. After a median follow-up of 21 months, one patient underwent a successful cardiac transplant and autologous stem cell transplantation (ASCT), while two other patients were in preparation for ASCT. Seven patients remained on daratumumab at the last follow-up. Two patients had infectious complications. There were no unexpected toxicities, and no grade III or IV adverse events, although more than half of our patients had advanced cardiac stage. Daratumumab induces deep and rapid hematologic response in newly diagnosed and previously treated AL amyloidosis patients. Intravenous administration is tolerated, even in patients with advanced heart disease.

P-232: Adverse event patterns and management with pomalidomide, dexamethasone, and daratumumab in patients with relapsed or refractory multiple myeloma: a safety analysis of the phase 2 MM-014 study

P-232: Adverse event patterns and management with pomalidomide, dexamethasone, and daratumumab in patients with relapsed or refractory multiple myeloma: a safety analysis of the phase 2 MM-014 study

P-270: GO41036: a Phase Ia/Ib open-label, multicenter study evaluating the safety and pharmacokinetics of tiragolumab in combination with atezolizumab and daratumumab in patients with R/R MM

P-270: GO41036: a Phase Ia/Ib open-label, multicenter study evaluating the safety and pharmacokinetics of tiragolumab in combination with atezolizumab and daratumumab in patients with R/R MM

P-199: Real-world duration of use and dosing frequency of daratumumab in patients with multiple myeloma in the U.S.

P-199: Real-world duration of use and dosing frequency of daratumumab in patients with multiple myeloma in the U.S.