Daratumumab Infusion Research Articles

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma.

With the increasing use of daratumumab (DARA)-containing regimens for multiple myeloma (MM) patients in China, the standard infusion time of DARA is long, with the potential for infusion-related reactions (IRRs) and increased hospitalization and use of resources. Shortening the duration of DARA infusion helps to optimize the hospital stay and enhance the patient treatment experience. The current, commonly used 90-min rapid DARA infusion regimen may not be applicable to Chinese MM patients, and therefore, we explored a new 110-min rapid DARA infusion regimen aimed at reducing the treatment burden on patients to guarantee therapeutic safety. MM inpatients treated with the DARA regimen were divided into two groups according to the number of times the DARA regimen was used: a standard infusion regimen for patients treated with the first two doses of DARA and a 110-min rapid infusion regimen for patients treated with more than two doses of DARA. Anti-allergy medications were routinely administered prior to the start of DARA infusion, patient consent, and authorization was obtained for all treatments, and statistical evaluation of the results was conducted via descriptive analyses, one-way ANOVA and chi-square tests. A total of 129 patients were included in this study: 68 in the standard infusion group, with 121 DARA infusions, and 129 in the rapid infusion group (patients who participated in the standard infusion subsequently participated in the rapid infusion), with 738 DARA infusions. The incidence of IRRs was 27.27% (36/121) in the standard infusion group and 1.35% (10/738) in the rapid infusion group, which were significantly different (p < 0.001). The incidence of IRRs after rapid infusion in other studies was <6%. The incidence of grade 1 IRRs in the rapid infusion group was 0.81% (6/738), the incidence of grade 2 IRRs was 0.54% (4/738), and there were no IRRs above grade 3; age, sex, and underlying disease had no effect on the choice of infusion method (p > 0.05). The mean infusion time after the occurrence of IRRs was also shorter in the rapid infusion group than in the standard infusion group (F = 24.781, p < 0.001). The 110-min rapid infusion DARA regimen is feasible and safe for use in Chinese MM patients.

#2748 Combined rituximab and daratumumab treatment in difficult to treat nephrotic syndrome cases

Abstract Background and Aims Common treatments for multidrug-resistant and multidrug-dependent nephrotic syndrome (NS) are inconsistently effective and burdened by long-term toxicities. Moreover, affected patients are at high risk of progression to end-stage kidney failure. Objective To test the safety/efficacy profile of combined single infusion of rituximab and daratumumab in inducing proteinuria remission in multidrug resistant nephrotic syndrome and maintaining drug free disease remission in patients with multidrug-dependent nephrotic syndrome after removal of oral immunosuppression. Method We here present a Phase 2 Proof-of-Concept single-arm clinical trial, that enrolled consecutive participants at the Nephrology Unit of the IRCCS Giannina Gaslini Children's Hospital in Genoa, Italy, between September 2021 and March 2023. Enrolled patients, aged between 3 and 24 years, were multidrug-dependent or multidrug-resistant nephrotic syndrome for at least 12 months before enrolment. Multidrug-dependency was defined by the need of at least 2 oral immunosuppressive drugs (prednisone and/or calcineurin inhibitors and/or mycophenolate mofetil) and by the occurrence of at least two consecutive relapses on two immunosuppressive drugs. Multidrug-resistance nephrotic syndrome was defined by the lack of antiproteinuric effect of a double immunosuppressive therapy. Exclusion criteria included genetic forms of NS and administration of monoclonal therapies in the last 9 months before enrolment. Interventions: Rituximab and daratumumab were administered as single doses at 375 mg/m2 and 16 mg/kg, respectively, 15 days apart. Main Outcomes and Measures:Proteinuria, serum albumin, Immunoglobulin M and G, B and T lymphocyte subsets, safety, Quality of Life. Results A total of 7 consecutive multidrug-resistant and 16 multidrug-dependent NS, respectively, were enrolled. In multidrug-resistant NS, combined rituximab and daratumumab promoted complete or partial remission in 6 patients (Fig. 1A). Five subjects experienced proteinuria relapse, that was effectively treated with a second course of combined treatment. Decreased of I'm, but not IgG, correlated with improvement of proteinuria (Fig. 1B).These treatment allowed to reduce the chronic immunosuppressive treatment daily administered (Fig. 1C). In multidrug-dependent NS, combined rituximab and daratumumab extended the relapse-free time, allowing us to remove oral immunosuppressant (Fig. 1D). Disease relapse was invariably anticipated by a recovery of circulating IgM:patients with IgM levels below median values measured at 3 mo post-treatment had a significantly lower rate of relapse at 9 mo than patients with higher IgM levels at 3 mo (Fig. 1E). Combined treatment induced significative reduction of CD38+ plasma cells (Fig. 1F) and IgM, but not IgG. Treatment was well tolerated and significantly increased quality of life. Conclusion Combined rituximab and daratumumab was safe and effective in the treatment of complicated forms of NS, offering a new therapeutic option for this severe condition.

Daratumumab maintenance after autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma

Objective: This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed. Results: Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) . Conclusions: Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Use of daratumumab drug formulation for subcutaneous administration in multiple myeloma therapy: Literature review and clinical observation

Study of the molecular pathogenesis of multiple myeloma led to development and introduction of antitumor agents with new mechanisms of action and their combinations into clinical practice. According to several trials, use of anti-CD38 monoclonal antibody daratumumab as part of triplet therapies at an early stage leads to deep and long-term antitumor response, achievement of MRD-negative status, and, as a result, increased survival and improved prognosis in all patient subgroups. High effectiveness of daratumumab subcutaneous formulation close to intravenous formulation has favorable safety profile, short administration time and low rate of infusion reactions which improves patients’ quality of life, affects their treatment compliance, and decreases healthcare costs.We present a clinical observation of a 60-year-old patient with newly diagnosed multiple myeloma who previously underwent treatment for another lymphoproliferative disorder which included autologous hematopoietic stem cell transplantation leading to complete and long-term remission. After 9 intravenous daratumumab infusions (with recommended dose of 16 mg/kg) in accordance to the D-Rd regimen, evaluation of antitumor effect and consideration of socially active lifestyle of the patient, daratumumab formulation for intravenous administration was replaced with subcutaneous formulation of fixed dose 1800 mg. Further deepening of the antitumor response was observed along with manageable safety profile and absence of significant adverse events which allowed to maintain intercourse intervals and improve the patient’s quality of life.

Outcomes of Incorporating IV Daratumumab for the Treatment of AL Amyloidosis in Real World Patients from a Multicenter Registry in Latin America

Introduction: AL amyloidosis is characterized by the extracellular deposition of immunoglobulin light chains. Daratumumab is an anti-CD38 monoclonal antibody that has demonstrated outstanding results in the treatment of AL amyloidosis, achieving rapid and deep responses and improving OS. Nevertheless, patients with advanced cardiac disease have been usually excluded from clinical trials and data from real world patients in Latin America is lacking. Moreover, subcutaneous Daratumumab is not available in most countries in the region. Objective: To describe hematological (HR) and organ response, overall survival (OS) and event-free survival (EFS) of incorporating IV Daratumumab for the treatment of AL amyloidosis in real world patients from 5 centers in Argentina Materials and methods: Multicenter, retrospective cohort study of patients older than 18 years with a histopathological diagnosis of AL Amyloidosis and treated with at least one cycle in first-line (Group 1) or subsequent lines of treatment (Group 2) with Daratumumab IV, included in the registry of amyloidosis (RIA, NCT01347047). Data were collected from medical records in an standardized electronic clinical report form (RIA Redcap). The registry includes data for baseline demographics, medical history, comorbidities, physical examinations, laboratory, and imaging exams. Treatments were prescribed by the physician, according to the hospital's protocol. All patients were followed from first daratumumab infusion till death or lost to follow up for HR (as per response criteria by the International Amyloidosis Society, complete response [CR], very good partial response [VGPR], partial response [PR], no response [NR]), OS (time from diagnosis to death), progression free survival (PFS: time from diagnosis to disease progression or death). Adverse events were reported based on CTCAE. Overall and progression-free survival was estimated using Kaplan Meier. Results Thirty-seven patients with AL amyloidosis were included in the study. The characteristics of the population are summarized in Table 1. Twenty-four patients (65%) had cardiac involvement, 25 (68%) renal involvement, and 14 (40% ) both. Of the patients with cardiac involvement, 20 had cardiac stages Mayo 2012 III/IV. Group 1 included 18 patients who received daratumumab (48%), 17 in combination with CyborD. Group 2 included 19 patients (51%), 12 received Daratumumab in combination with dexamethasone, 5 with CyborD and 2 with lenalidomide. Thirty-three patients (90%) achieved HR, the median time to best hematologic response was 2 months (IQR 1-9 months). Seventeen patients (59%) achieved CR (group1 n=8 Group2 n=9), 9 MBRP (group1 n=4 group2 n=5), 7 PR (group1 n= 5 group2 n=2). Of the 20 patients with Mayo stages III/IV, 18 achieved hematologic response and 9 cardiac response. Three patients had stable disease, all of them were relapsed.. Three patients presented subsequent relapses. The Organ response rate was 59% (n=22, IC 45-75), 14 renal response, median time to response 8 months (IQ R4,6-14,1), 13 cardiac response, median time to response 6,4 months (IQR 6,4-6,4). Five patients had response of both organs. The median follow-up of the entire cohort was 18 months (CI 11-75). The median EFS at 1 year was 88% (CI 71-95) and at 2 years 83% (CI 64-93). Median OS at 12 months was 91% (CI 75-97) and at 24 months 86% (CI 68-95). There were 7 deaths in the entire cohort, 5 were due to cardiac complications associated with amyloidosis. Five of the deceased patients had achieved a HR. Eleven patients presented adverse events, mainly infectious complications, 5 of them grade 3 or 4. Conclusions: This study provides real-world evidence for Daratumumab IV treatment in patients with AL amyloidosis in the first line and at relapse, achieving fast and profound HR, which translated into a high organ response rate and improvement in OS and PFS. In our cohort, most patients achieved HR with a median time to best response at 2 months consistent with what is reported in the bibliography. This study is relevant since it is a real life study, in which intravenous daratumumab was used since the subcutaneous formulation is not available in most Latin American countries and also included patients with advanced stages achieving responses in this high risk subgroup. Treatment with Daratumumab should be considered a therapy of choice in AL amyloidosis, even in patients with advanced cardiac stages.

Addressing hypersensitivity reactions induced by Daratumumab: A review of management approaches and preventive measures

Daratumumab is a novel and remedial monoclonal antibody with broad-spectrum killing activity. It has shown a favorable safety profile as monotherapy in cases with relapsed/refractory multiple myeloma. Daratumumab along with its remedial benefits is associated with a range of Adverse Drug Reactions (ADRs) most importantly Hypersensitivity reactions that can significantly impact patient outcomes and health-related quality of life. The standard of care can be maintained by administering pre-infusion prophylactic medications and also by optimizing the Daratumumab infusions. The review focuses on the adverse drug reactions induced by Daratumumab, various preventative measures, and management strategies opted for curbing the Daratumumab-mediated infusion-related hypersensitivity reactions.

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.

Avoiding Daratumumab Interference with Blood Typing

Background Daratumumab is an IgG monoclonal antibody that binds CD38 on hematopoietic cells and induces apoptosis. It is FDA approved for upfront treatment of systemic light chain amyloidosis as well as treatment of frontline and relapsed/refractory multiple myeloma. Daratumumab, similar to other CD38 monoclonal antibodies, interferes with blood compatibility testing by causing panagglunination on the Indirect Antiglobulin Test (IAT) leading to false positive results and delays in blood availability for transfusion. This panagglutination can persist up to 6 months after the last Daratumumab infusion. Additionally, attempts to overcome this may mask the presence of a clinically significant antibody resulting in acute or delayed hemolytic transfusion reactions. Several laboratory techniques like RBC genotyping, phenotyping, and the use of Dithiothretol (DTT) treatment of serum are used to overcome this laboratory abnormality. These are either technically time consuming or not widely available in all healthcare institutions. DTT, though readily available, requires prior notification of the blood bank when a patient who is being treated with Daratumumab needs a transfusion. This labor intensive and time consuming process may result in delays in patient care adverse outcomes. By far, the most cost effective way is to obtain blood type and antibody screen (IAT) prior to the initial Daratumumab administration. However, this requires institutional strategy (policy, procedure and pathway) for all potential patients starting anti CD38 monoclonal antibodies in general and daratumumab in particular, to allow timely typing and screening of blood in preparation for future transfusion needs. This quality improvement project was instituted to obtain a type and screen (T&S) prior to patients starting Daratumumab in order to champion high value healthcare which balances clinical benefit with costs and harms with the ultimate goal of improving patient outcomes. Methods and Results We retrospectively identified 32 patients who received their first Daratumumab infusion or subcutaneous injection from 11/1/2017 to 5/31/2020 at Community Medical Centers and Community Cancer Institute in Clovis, California and Fresno, California. 13 patients did not have a T&S done within 30 days prior to initiation of Daratumumab, which translates to 40.6%. We conducted manual chart of all patients prior to the intervention and found 6 patients without prior T&S who required transfusions after starting Daratumumab. Each transfusion was regarded as an event regardless of the units of blood received. We calculated the time from T&S order to receipt of transfusion. In total, there were 15 events which amounts to 1,5990 cumulative minute, with the average time to transfusion (TTT) being 1066 minutes. There were also 6 patients with T&S performed prior to Daratumumab initiation who had a total of 22 transfusion events that took 20417 minutes. The average TTT for this group is 928 minutes. The difference in average TTT between patients who had T&S and those that did not have T&S is 138 minutes, which can be clinically significant. We implemented a T&S as part of "Day 0" in our chemotherapy orders in December 2020. 17 patients received their first Daratumumab from January 2021 to January 2022. 15 patients (88%) had T&S performed and 2 patients did not as they were patients from out of network providers. Conclusion We are continuing to gather additional data to see if this improvement results in a decrease in average TTT post implementation. This is quality improvement project represents a major step in reducing delays in blood compatibility testing due to Daratumumab. There are no significant changes in resource utilization since patients who need transfusions will require a T&S to be done regardless. Ensuring that a T&S is performed antecedent to the first Daratumumab treatment will reduce delays in obtaining matched blood products for our myeloma patients. This supports timely transfusions to lower adverse outcomes associated with anemia due to chemotherapy and multiple myeloma.

How to Treat Isolated Leptomeningeal Relapse of Multiple Myeloma 11 Years after Autologous Stem Cell Transplantation (ASCT)

Post transplant relapse of Multiple Myeloma (MM) in the central nervous system (CNS) is rare and it is almost always associated with systematic relapse and in most instances, shortly after initial treatment. We did not encounter reports of relapse isolated to the CNS ten years post-transplant. In October 2009, a 49-year-old male presented with an IgG lambda MM, ISS II. He was treated with Bortezomib/Dexamethasone, autologous PBSCT, followed by two years maintenance with Lenalidomide, attaining stringent CR, confirmed by PET/CT. He discontinued follow up and returned after 11y/8m progression free survival, in June 2021 with paraplegia due to cauda equina syndrome. NMR consistent with leptomeningeal infiltration, single focal intramedullary lesion at L1 level without bone affectation. No MM defining criteria (CRAB). Normal levels of serum Immunoglobulins (IGs), serum and urine immunofixation, and serum free light chains. Flow cytometry negative in bone marrow. Spinal tap was unsuccessful and through an Ommaya reservoir, that was placed after NMR showed evidence of cranial leptomeningeal involvement, CSF showed infiltration by countless malignant plasma cells. Patient received immediate conformational radiotherapy and biweekly IT methotrexate and hydrocortisone. A month later his course was complicated by left leg proximal deep vein thrombosis and pulmonary embolism which was treated with Apixaban. Given the rarity of this type of relapse, we questioned the appropriateness of the treatment and searched the literature with respect to the accessibility of the CNS by the different novel drugs used to treat MM in order to determine the most effective strategy. In addition to corticosteroids, there is clinical evidence that thalidomide crosses the blood-brain barrier (BBB), in murine models pomalidomide also has good penetration into the CNS. Both have a penetration of 30 to 40% into the CSF. Among proteasome inhibitors, only marizomib has been observed to cross the BBB in a murine model, while bortezomib does not. With respect to anti CD38 monoclonal antibodies, mass spectrometry at 12, 15, and 19 days after daratumumab infusion showed antibody levels in CSF 71 times less than in serum on the three sample days. It is not known if weekly doses of daratumumab could attain therapeutic levels in CSF. We found only 14 cases of isolated CNS relapse in patients with MM treated with ASCT with a median interval between transplant and relapse of 3 months (0.5-96m), with only one reported relapse 7.5 years after autologous transplant and the median overall survival was only 3 months. Two cases died in less than a month and only one case survived for a year after the CNS relapse.To date, our patient has received 12 cycles of Pomalidomide/dexamethasone with progressive improvement, now he is able to carry on his life unassisted and there is no evidence of MM relapse anywhere. The rarity of this case scenario highlights the lack of knowledge regarding the best approach to CNS MM relapse. There is no evidence of the effectiveness of methotrexate and Ara C, in MM, and no novel drug can be instilled into the CSF. We conclude that the systemic use of pomalidomide and dexamethasone should be the best approach of MM isolated CNS relapse. Further investigations will clarify if other novel drugs are active in this context.

Targeting C3d in Combination with Daratumumab:a Strategy to Enhance Therapeutic Potential in Multiple Myeloma

The monoclonal antibody (mAb) daratumumab (DARA) targeting CD38 can induce minimal residual disease negative remissions in patients with multiple myeloma (MM). However, majority of patients subsequently relapse or become refractory to treatment (RRMM). Rapid reduction of surface CD38 levels in MM cells following DARA infusion due to trogocytosis by monocytes and granulocytes leads to reduced complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC), effector functions that rely on antigen density. High expression of complement regulatory proteins, CD55 and CD59 on MM cell surface can also impede CDC activity. Therefore, modalities to overcome these limitations and improve clinical outcome for patients with RRMM are needed. Daratumumab is a strong activator of complement. While a subset of cells may be lysed by the membrane attack complex, all cells reacted with daratumumab are opsonized by C3d, the terminal component of C3. C3d remains covalently attached at the cell surface. Thus, the newly acquired membrane bound C3d constitutes a target for additional intervention, particularly when the cell surface CD38 is lost or low following treatment with DARA. Using phage display technology, we generated and characterized recombinant rabbit/human chimeric mAbs that selectively bind C3 fragments including C3d but not full length C3. We selected two high affinity anti-C3d mAbs (clones 5S8 and d301 with kD values 3.35 nM and 0.99 nM, respectively) that showed reactivity against both human and mouse C3d. To deposit C3d on myeloma cell lines (MM1-S, MM1-R, RPMI8226, NCI-H929, KMS-12-PE) without activating CDC, the cells were reacted with DARA in C5 depleted normal human serum. Both 5S8 and d301 bound to the C3d opsonized cells. Based on SPR analysis these two mAbs do not compete for C3d binding suggesting that they recognize distinct epitopes. In normal human serum, the anti-C3d mAbs enhanced killing by CDC of DARA-opsonized target cells compared to DARA alone (P<0.0001). The non-targeting IgG1 isotype control mAb trastuzumab (TRA) did not bind C3d or enhance DARA-mediated killing. To test the combination of DARA with anti-C3d mAbs in vivo, we used Balb/c-SCID mice bearing subcutaneous (s. c.) MM1-R tumors. First, using clones 5S8 and d301, we demonstrated in vivo binding of mouse C3d on MM1-R tumor cells harvested 24 h after a single intraperitoneal (i. p.) injection of DARA. Next, we challenged the mice s. c. with MM1-R cells and randomly divided them into the following treatment groups: 20 mg/kg DARA single agent (n=7), or combination treatments of 10 mg/kg of each of two mAbs: DARA + TRA (n=10), DARA + 5S8 (n=13), DARA + d301 (n=13). The mAbs were given via i. p. injections weekly starting on day 7 post tumor challenge and continued for 6 weeks. Palpable tumors were noticed in mice between days 7 and 14, and tumor growth was monitored by caliper measurements twice weekly. Mice were euthanized when tumors reached pre-defined limits. All the mice that received DARA + TRA showed progressive tumor growth with median survival of 38 days and all mice had to be euthanized by day 50. Doubling the dose of DARA to 20mg/kg slightly increased median survival to 43 days (P = 0.12 vs DARA+TRA). Two of 7 mice that received DARA alone (at 20 mg/kg) survived to day 175. Median survival for mice treated with DARA (10mg/kg) plus an anti-C3d mAb was 162 days (P = 0.006 for comparison to DARA 20mg/kg), and 13 of 26 (50%) mice in this cohort survived tumor-free beyond 200 days. There was no statistically significant difference between groups treated with 5S8 or d301 in combination with DARA (P = 0.23). All the surviving mice showed no evidence of tumor, weight loss or other morbidity indicating that they are essentially tumor-free. In summary, these results demonstrate that combination treatment of DARA with anti-C3d mAbs improves efficacy over single agent DARA leading to long-term survival in the MM.1R xenograft model. The combination of C3d targeting mAbs with DARA could improve clinical efficacy and overcome resistance to single agent therapy.

Safety and efficacy of daratumumab use in patients with renal impairment and hemodialysis.

8026 Background: Targeting CD38 in multiple myeloma (MM) using daratumumab-based regimens can prolong remission in both the newly diagnosed and relapsed settings. However clinical trials have excluded patients with creatinine clearances (CrCl) &lt;30 mL/min, warranting real-world analysis of daratumumab use in MM patients with renal insufficiency. Methods: Following IRB approval, we performed a retrospective chart review of relapsed MM patients at our institution who had reduced CrCl and received at least one dose of either daratumumab between October 2018 and January 2022. All subjects received IV daratumumab, 52% went on to receive SQ. Outcomes included change in CrCl during treatment, adverse events, and survival. Survival was estimated using product-limit estimates. CrCl groups at daratumumab initiation of more or less than 30 were compared using the chi-square test or Fisher’s exact test, as deemed appropriate, for categorical variables and the two-sample t-test or Mann-Whitney test for continuous data (SAS Institute Inc., Cary, NC). Results: 101 MM patients were included, with median age of 74 (54-92); 46 (45.5%) were female. 14% were on hemodialysis. Patients had a median of 2 prior lines of therapy. Distribution of R-ISS stages were I (20%), II (35%), and III (45%). High-risk cytogenetics were present in 20%. A median of 23 daratumumab infusions (1-60) were delivered over a median of 18 months (median IV=16, SQ=10). Daratumumab regimens included DRD (32%), DPD (35%), DKD (13%), and DVD (35%). Median CrCl at MM diagnosis and at daratumumab initiation was 45 (7.3-101) and 40 (5.3-107), respectively, with 33% having CrCl &lt;30. Following 3, 6, and 12 months (n = 95, 89, 69) on daratumumab-based regimens, median CrCl were 45, 43, and 41, respectively. There were no differences in renal function in patients who went on to receive SQ daratumumab. 16 patients had died at the time of data collection, and the median survival was 63 months. Of the 101 patients, 16 subjects were deceased at the time of data collection, and 23% of subjects had gone on to subsequent treatments. Analysis showed that there was a progression-free survival of 54% at 5 years. The most common adverse events reported were anemia (37%) and neutropenia (15%). Infusion-related reactions were reported in 19% of patients. Conclusions: This is the largest real-world assessment of outcome for MM patients treated with daratumumab-containing regimens in the setting of renal insufficiency. There was no significant impact of the treatment on renal function at 12 months. Compared to published data on patients treated with CrCl&gt;30, there does not appear to be a detriment to survival or an increase in adverse events when using daratumumab regimens in patients with more advanced renal insufficiency.

Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma.

BackgroundThe anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019.MethodsWe conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs.ResultsA total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol.ConclusionsOur findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.

Characteristics of Daratumumab Reactions in Patients Who Transitioned from Intravenous Daratumumab to Subcutaneous Daratumumab

IntroductionDaratumumab based therapy has become standard of care in the treatment of Multiple Myeloma and Systemic Light chain Amyloidosis. The intravenous (IV) infusion of daratumumab is associated with a high rate of infusion-related reactions necessitating use of rescue medications and prolonged chair time. The Phase 3 COLUMBA trial reported non-inferiority of the subcutaneous (SC) daratumumab as compared to IV formulation with significantly reduced rates of daratumumab reactions for new-start patients. However, there is limited data on the characteristics of reactions in patients transitioning between formulations.MethodsThis single center retrospective chart review was performed on consecutive patients who previously received IV daratumumab but subsequently converted to SC daratumumab between June 2020 and June 2021. In this study, severity of allergic reactions and potential predictors of SC daratumumab reaction were assessed.ResultsOf the 45 patients who received SC daratumumab during the study period, a total of 13 patients had previously received IV daratumumab. All patients were premedicated per package insert guidelines and institutional standard of care. Patients were predominately Caucasian (77%), Male (84.6%), and undergoing therapy for Multiple myeloma (69%) and AL Amyloidosis (31%). A mean of 19 doses of IV daratumumab were administered prior to transition to SC formulation. The majority of patients (53.8%) transitioned to SC daratumumab had previously reacted to IV daratumumab. All IV daratumumab reactions occurred during the first infusion. Two patients had experienced Grade 3 reactions to IV daratumumab, requiring inpatient observation to complete the initial infusion but tolerated subsequent doses.Of the 13 patients transitioned to SC daratumumab, two patients (15.4%) experienced daratumumab reactions. Patient 1 had a history of grade 3 IV daratumumab reaction to the first infusion and experienced a Grade 2 reaction at 3 hour 50 minutes with symptoms of cough, shortness of breath, palpitations, itching, and myalgia to the first SC daratumumab dose. Subsequent SC daratumumab doses were tolerated without adverse reactions. The other patient had a history of grade 2 IV daratumumab reaction who noted worsening weakness and diarrhea in the first several days post-injection with the new formulation, and ultimately transitioned back to the IV formulation.ConclusionAlthough SC daratumumab is well tolerated in patients previously treated with IV daratumumab, patients with history of prior first IV daratumumab infusion reactions are still at increased risk of early or delayed daratumumab related reactions with first time exposure to SC daratumumab. DisclosuresGupta: Deva Oncology: Consultancy. Raza: Amgen: Honoraria, Speakers Bureau; drrx, acasti, amicus, abbot: Other: previous stock holder (currently does not hold these stocks); Gilead: Current holder of individual stocks in a privately-held company; Janseen: Honoraria, Speakers Bureau; Takeda: Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Moderna , Biontec, Stryker: Current holder of individual stocks in a privately-held company; novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Speakers Bureau.

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Successful Conversion and Implementation to Subcutaneous Daratumumab in Patients with Multiple Myeloma (MM) and Light Chain (AL) Amyloidosis

IntroductionIntravenous (IV) daratumumab has become a standard in the treatment of MM and AL amyloidosis largely due to its significant clinical benefit. Due to the high risk of infusion-related reactions (IRRs) prolonged infusion times are required at time of treatment initiation. These lengthy administrations can limit clinic capacity, require split dose infusions, increase chair time, and decrease patient satisfaction. Fixed-dose subcutaneous (SC) formulation of daratumumab (daratumumab and hyaluronidase-fihj) was approved in 2020 for the treatment of MM and subsequently, AL amyloidosis in 2021. While landmark trials have demonstrated its efficacy, there is lack of consensus around the standardized pre-medications and post-injection monitoring times for SC daratumumab. We present real world evidence from a large academic center with adoption and standardization of SC formulation of daratumumab into clinical practice.MethodsWe evaluated all patients that received SC daratumumab for MM and/or AL amyloidosis at Boston Medical Center from June 1, 2020 to February 28, 2021. Baseline demographics were collected, including patient diagnosis, chemotherapy regimen, prior daratumumab administration details, and total doses of daratumumab received. Patients that were naïve to daratumumab, started their first dose as a SC injection. Patients were monitored for 30 minutes following the first SC dose and were pre-medicated with all oral agents: acetaminophen, dexamethasone, and diphenhydramine. Infusion chair time, improvement in clinic efficiency (using our standard infusion time of 90 minutes for IV daratumumab infusions after the 2nd dose), and safety were evaluated.ResultsA total of 41 patients were treated with SC daratumumab. Eighteen patients (44%) were switched from IV daratumumab to SC daratumumab. All other patients were naïve to SC daratumumab (n=23). All patients were monitored for 30 minutes after their first SC daratumumab dose only. In the absence of an ARR (administration-related reactions), patients were not monitored after subsequent injections. One patient had facial and neck swelling 2 days after administration of SC daratumumab (with no other symptoms) but resolved within 24 hours of an additional dose of dexamethasone and did not recur upon re-challenge of SC daratumumab. One patient experienced nausea following her first dose of SC daratumumab but it resolved without intervention. All patients received dexamethasone 20-40 mg (as anti-myeloma dose), acetaminophen 650 mg, and diphenhydramine 25-50 mg prior to the dose of SC daratumumab. Fourteen patients (24%) received montelukast 10 mg and 19 patients (46%) received famotidine 20-40 mg prior to the dose of SC daratumumab at provider discretion. Dexamethasone 4 mg daily for two days post-injection was not administered with SC formulation as was previously routine with the IV formulation. When analyzing the chair time saved by this standard monitoring protocol, a total of 478.8 hours of chair time were saved that were used for other patients in our practice (average of 11.7 hours saved per patient).ConclusionWe report a successful conversion and adoption of SC daratumumab at our ambulatory hematology/oncology clinic. A standard 30-minute monitoring parameter can safely be implemented following the first SC daratumumab dose. Furthermore, less aggressive supportive medications can also be used. Integration of the SC formulation yielded significant chair time savings and may have the ability to create a more efficient clinic workflow. [Display omitted] DisclosuresHughes: Rigel: Other: Advisory Board, Research Funding; Amgen: Speakers Bureau; Karyopharm: Other: Advisory Board, Speakers Bureau; Abbvie: Speakers Bureau. Sloan: Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Stemline: Honoraria. Sanchorawala: Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Pfizer: Honoraria.

P-130: The impact of COVID-19 on the treatment regimens of myeloma and AL amyloidosis patients

BackgroundAs the COVID-19 pandemic unfolded in 2020, Myeloma Patients Europe (MPE) recognized that the pandemic was impacting the healthcare and lives of people with myeloma and AL amyloidosis, and their caregivers. Findings from a small UK study suggested that myeloma patients were more likely to die from COVID-19 than members of the general population who contracted the virus [Cook et al, 2020]. Focus groups were conducted to learn more about the impact of COVID-19 on the lives of patients and their families, with a focus on its impact on diagnosis and treatment.MethodMPE researchers conducted four online focus groups in Europe examining the views and experiences of myeloma and AL amyloidosis patients and caregivers during the COVID-19 pandemic. Fifteen patients and two caregivers took part. Thirteen patients had myeloma and two had AL amyloidosis. Participants were from Spain (n = 6), the UK (n = 2), Belgium (n = 2), Germany (n = 2), the Netherlands (n = 1), Iceland (n = 1), Israel (n = 1), Poland (n = 1), and Romania (n = 1). Eleven patients had been diagnosed within the last few years, while four were living with myeloma for a decade or longer. Ten patients were receiving active treatment for myeloma or AL amyloidosis during the pandemic, while others were in remission.ResultsSixty percent of study participants reported that the COVID-19 pandemic negatively affected their treatment. Three patients said that medicines given in hospital (by infusion or injection) were delayed due to COVID-19 restrictions. Sometimes, the frequency of these treatments was reduced. In contrast, most patients taking oral medicines (tablets) reported that their treatment continued as normal. Seven participants said their or another patient’s invasive procedure (such as a bone marrow biopsy or stem cell transplant) had been delayed. These procedures took place after approximately 1–6 months later than originally scheduled, once HCPs and patients felt it was safe to do so. One patient reported an improvement in her treatment due to the pandemic restrictions. Her 4- to 5-hour long infusions of daratumumab in hospital had been switched to subcutaneous injections with fewer side-effects.ConclusionsFindings suggest that COVID-19 had an impact on patients with myeloma and AL Amyloidosis and their treatments. Some aspects of this may be positive, with preference data showing that patients have a preference for oral administrations (Fifer et al, 2020) and as such, switching patients to at home treatment regimens may have both avoided treatment delays and also been in line with patient preferences for treatment administration. MPE suggest that the administration of treatments should be examined regularly. COVID-19 upended existing treatments and other healthcare services, but patients and their healthcare providers should be reviewing options on an ongoing basis to ensure both high quality of care and changes in patient preferences over time.

Ninety-Minute Daratumumab Infusion Is Safe in Multiple Myeloma

▪Background: Daratumumab, an anti-CD38 monoclonal antibody, was first approved for the treatment of relapsed and refractory multiple myeloma (MM) in December of 2015. The approved initial infusion lasts at least 6.5 hours, second infusion for 4.5 hours and all subsequent infusions over 3.5 hours. The risk of infusion related reactions (IRRs) is very low after the second infusion, and the prolonged continued infusion time results in long days for patients. Because of our success infusing other monoclonal antibodies over shorter times, such as rituximab (Dotson et al Support Care Cancer, 2016), we hypothesized that shortening the daratumumab infusion from 3.5 hours to 90 minutes beginning with the third infusion would not increase the incidence of IRRs.Methods: This is a single-center safety study of an accelerated daratumumab infusion in patients receiving standard of care daratumumab therapy. Patients were eligible once they received at least 2 prior doses of daratumumab, administered per standard prescribing information. Previous IRR was not an exclusion criterion. The accelerated infusion was calculated to deliver 20% of the dose over the first 30 minutes, then the remaining 80% over 60 minutes, resulting in an estimated 90 minute infusion (Table 1). Patients who tolerated the infusion well were allowed to continue the accelerated rate. Premedication regimens were allowed to be altered based on previous tolerability. Simon's two-stage optimal design was utilized to design the study based on the incidence of grade 3 or above IRR. With 80% power the design allows 7 patients to be treated in the first stage, and if no patients experienced ≥ grade 3 IRR, an additional 21 patients would be treated. Out of all 28 patients, if 2 or more experienced ≥ grade 3 IRR, the regimen would be declared as too toxic. The protocol was approved by the cancer institutional review board.Results: Baseline characteristics are listed in Table 2. Twenty eight patients were treated with daratumumab utilizing the accelerated rate, 8 of which received the accelerated infusion with their third dose of daratumumab. The premedication regimen varied patient-to-patient and did not impact tolerability of the accelerated infusion. There were 5 patients who did not receive any steroid premedication and 3 who received reduced doses (< 12 mg) of dexamethasone. Of the 28 patients treated, there was only 1 adverse reaction - a grade 2 hypertension during which the infusion was paused for a patient that had received 10 prior infusions at standard rates. The patient received a diuretic, the infusion was resumed and subsequently increased to the accelerated rate without further incidence of hypertension. There were no grade 3 or higher IRRs. At the 4-week follow-up, all patients remaining on daratumumab treatment continued at the accelerated infusion rate.Conclusion: An accelerated infusion rate of daratumumab delivering 20% of the dose over 30 minutes and 80% over 60 minutes is feasible and well-tolerated in patients who have received 2 prior doses of daratumumab at standard infusion rates. Starting with the third dose of daratumumab therapy, the 90-minute infusion is now standard practice at our institution. [Display omitted] DisclosuresHofmeister:Janssen: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Karyopharm: Research Funding; Celgene: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Thrassos: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Daratumumab Monotherapy in Thirty-Two Heavily Pre-Treated Patients with Advanced Systemic Light-Chain Amyloidosis

BackgroundSystemic light-chain amyloidosis (AL) is a life-threatening disease caused by the misfolding and deposition of clonal free light-chains (FLC). The current standard of therapy is targeting the malignant plasma cells with chemotherapy to reduce the circulating FLC burden.Daratumumab is a human monoclonal IgG kappa antibody targeting CD38 which is mainly expressed on plasma cells. It has been approved as a monotherapy in the European Union in May 2016 for treatment in patients with multiple myeloma (MM) exposed to proteasome inhibitors (PI) and immunomodulatory drugs (IMID). Sher et al. (Blood 2016) first published a case report with an FLC response in a patient with cardiac AL and a hematologic complete remission (CR) in a patient with renal AL. Kaufman et al. (Blood 2017) reported a hematologic response (>PR) in 19 of 25 pretreated patients with systemic AL.Patients and MethodsThis is a retrospective analysis of 32 consecutive patients treated with daratumumab monotherapy starting from October 2016 for symptomatic AL at our institution. Only patients with an underlying MM (smoldering or CRAB+) were initiated on daratumumab. Hematologic remission and NT-ProBNP response were assessed according to Palladini et al., JCO 2012, renal response according to Palladini et al., Blood 2014. Daratumumab 16 mg/kg of total body weight was applied intravenously after premedication with dexamethasone (commonly 20 mg), intravenous paracetamol and antihistamine. Infusions were initiated weekly in 17 patients and every other week in 15 patients due to reduced performance status. For evaluation of hematologic progression-free survival (PFS) the addition of a second therapeutic agent was also considered as an event. Hematologic PFS was calculated using SPSS v.24.0 statistical software (IBM, Armonk, New York, USA)Patient cohort: For patient characteristics please refer to the tables .ResultsHematologic response: Twenty-three of 32 patients achieved a hematologic remission after a median duration of 49 days (range: 5-287). Patients received a median of 8 (range: 2-17) infusions of daratumumab. CR was achieved in 3 patients, a very good partial remission (VGPR) in 14 and a partial remission (PR) in 6 patients (see figure).The 3 month overall response rate among 27 evaluable patients was 63% with CR in 3 patients, VGPR in 10 patients and PR in 4 patients.Progression and survival: After a median follow-up time for patients alive of 134 days from the first daratumumab infusion median PFS is not reached (figure). Currently, 21 patients are still on and four patients are off therapy without hematologic progress. One patient died from a cardiac event after discontinuing daratumumab for no response. Another patient with a VGPR died after infectious complications.Organ response at 3 months: For 14 of 25 patients with cardiac AL NT-ProBNP analysis was performed. Two patients had an NT-ProBNP response and six patients had an NT-ProBNP increase. Renal response assessment was performed in 9 of 15 patients with renal involvement not on dialysis and showed a response in 3 patients and a progression in 3 patients.Complications: One patient with cardiac AL and terminal renal failure on peritoneal dialysis died after developing peritonitis after 90 days of first daratumumab infusion. Another four patients with cardiac AL were admitted to hospital for lower respiratory tract infections (3) or cardiac decompensation (1). Mild upper respiratory tract infections were reported in six patients. One patient newly developed atrial fibrillation. Two patients with symptomatic MM experienced dyspnoea during the first infusion. One patient with symptomatic MM required a blood transfusion.SummaryDaratumumab monotherapy can induce fast hematologic responses in heavily pre-treated AL patients who cannot tolerate or are refractory to proteasome inhibitors or immunomodulatory drugs. NT-ProBNP and renal responses can be achieved, although NT-ProBNP progression under therapy was common in our cohort. As expected, patients with advanced cardiac AL are at a higher risk of severe complications. [Display omitted] DisclosuresSchönland:Sanofi: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; prothena: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau. Hegenbart:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Prothena: Membership on an entity's Board of Directors or advisory committees.

Safety and Tolerability of Daratumumab in Patients with Relapsed Light Chain (AL) Amyloidosis: Preliminary Results of a Phase II Study

Daratumumab is a human IgG1k monoclonal antibody targeting the CD38 surface antigen on plasma cells, and has proven efficacy in multiple myeloma. AL amyloidosis is a plasma cell disorder in which clonal bone marrow plasma cells produce immunoglobulin light chains that misfold into fibrils that are deposited in organs, leading to organ dysfunction and failure. While the biology of the clonal plasma cell in AL amyloidosis is distinct from that of myeloma, clonal plasma cells in AL amyloidosis do express surface CD38, providing a rationale for the use of daratumumab in AL amyloidosis. Infusion reactions (IR) of 48% were reported in patients who received daratumumab as monotherapy for relapsed multiple myeloma. Therefore, we designed a clinical trial to study tolerability of daratumumab in patients with relapsed AL amyloidosis (clinicaltrials.gov identifier: NCT02841033). The primary objective was to determine the safety and tolerability of infusion of daratumumab, with respect to IR. The secondary objectives were to assess hematologic response, clinical response and time to next treatment.Accrual on this clinical trial started in April 2017. Patients with relapsed AL amyloidosis after ≥1 prior therapy, and involvement of at least one major vital organ , eGFR of >20 mL/min, AST/ALT < 3xULN, NTproBNP <8500 pg/mL, LVEF >30%, FEV1 >50% in patients with known COPD or chronic smokers, and ECOG performance status of <3, received daratumumab at 16 mg/kg IV infusion weekly for weeks 1-8, followed by every 2 weeks for weeks 9-24 and every 4 weeks thereafter until progression or unacceptable toxicities, for up to 24 months. The first infusion of daratumumab was administered in 1000 mL, the second infusion in 500 mL if no grade 1 or greater reactions occurred throughout the first 3 hours of the first infusion, and subsequent doses were administered in 500 mL of saline. All patients received acetaminophen, diphenhydramine, loratidine, famotidine, monteleukast and methyprednisolone (100 mg for the first 2 infusions and 60 mg thereafter) 30-60 minutes prior to infusion. Ondansetron was added after developement of grade 1 nausea/vomiting in the first 2 patients. Diphenhydramine, famotidine and methyprednisolone (40 mg) were also administered 2 hours after the start of infusion during the first 2 infusions even if there was no reaction. Methylprednisolone 20 mg (or its equivalent) and monteleukast were adminsitered 24 and 48 hours after start of infusion for the first 2 infusions and then monteleukast was optional. All patients received prophylaxis with acyclovir.At data cut-off (July 23, 2017) 8 patients have been enrolled. The median age was 63 years (range, 60-83), and median number of prior therapies was 3 (range, 1-6): 6 (75%) had received HDM/SCT, 5 (62.5%) had received immunomodulatory agents, and 7 (87.5%) proteosome inhibitors. Three patients were refractory to prior therapy and the median time from last therapy was 15 months. The median time from diagnosis to enrollment on this trial was 68 months. The median number of organ systems involved was 2 (range, 1-4). Five patients (62.5%) had involvement of >2 organ systems. All 8 (100%) patients had cardiac biomarker stage II or III disease. Median NT-proBNP level was 1650.5 pg/mL (range, 656-3962) and urine protein excretion was 0.41 g/24 h (range, 0-10.1), while median dFLC was 196.8 mg/L (range, 20.4-854). At the time of this report, 7 patients continue on study and a total of 65 infusions have been completed. The median number of infusions received per patient is 9 (range, 2-12). One patient was removed from the protocol after developing progression of plasma cell dyscrasia markers after 2 cycles. No patient experienced a grade 3-4 IR. Only 2 patients experienced grade 1 nausea and vomiting during first infusion, which resolved after an antiemetic, without experiencing IR. There was no interruption or delay of infusion. No hospitalization for IR was required. The median time of first infusion was 6.5 hours and 2nd infusion was 4.2 hours. Hematologic responses were rapid and are shown in Figure 1.Daratumumab infusion is well tolerated in patients with relapsed AL amyloidosis, when administered with appropriate pre and post-medications. Infusion related reactions were minimal and not comparable to reported incidence in myeloma. Preliminary data suggest a rapid hematologic response after 1 dose of daratumumab in patients with AL amyloidosis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety and Efficacy of Daratumumab Monotherapy in Patients with Heavily Pretreated Relapsed and Refractory Multiple Myeloma: Final Results from GEN501 and Sirius

Safety and Efficacy of Daratumumab Monotherapy in Patients with Heavily Pretreated Relapsed and Refractory Multiple Myeloma: Final Results from GEN501 and Sirius