Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results.

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing.

Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant.

BackgroundRefractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).MethodsIn phase I/II trials, we treated 67 subjects for CMV viremia or disease arising after HCT with adoptive transfer of banked, third-party, CMVpp65-sensitized T cells (CMVpp65-VSTs). All were evaluable for toxicity and 59 for response.

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter's transformation.

Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter's transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017.

Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes.

Purpose: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs).

Design: Retrospective cohort study.

Participants: Patients with active CMV retinitis evaluated at a tertiary care academic center.

Prognostic Factors for Postrelapse Survival after ex Vivo CD34-Selected (T Cell-Depleted) Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma.

Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT.

Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation.

BACKGROUNDAdoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.METHODSWe developed a third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs.

Ex Vivo T Cell-Depleted Hematopoietic Stem Cell Transplantation for Adult Patients with Acute Myelogenous Leukemia in First and Second Remission: Long-Term Disease-Free Survival with a Significantly Reduced Risk of Graft-versus-Host Disease.

Large series of patients with acute myelogenous leukemia (AML) after ex vivo T cell-depleted (TCD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) have not been reported previously. We retrospectively analyzed the outcomes of 266 patients (median age, 54 years) with AML who received CD34-selected TCD allo-HSCTs while in first (75%) or second (25%) complete remission (CR1/CR2) at a single institution. The conditioning regimens were all myeloablative, and no additional graft-versus-host disease (GVHD) prophylaxis was given.

Presalvage International Staging System Stage and Other Important Outcome Associations in CD34-Selected Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Despite ongoing therapeutic advances, multiple myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to immunomodulatory drugs or proteasome inhibitors remain grim. Allogeneic hematopoietic cell transplantation (alloHCT) is an alternative option that may offer potential for cure. Although rates of transplantation-related morbidity and mortality have decreased in recent years, weighing this approach's potential benefits against nontransplantation therapies demands a thoroughly informed pre-alloHCT assessment.

Revaccination after Autologous Hematopoietic Stem Cell Transplantation Is Safe and Effective in Patients with Multiple Myeloma Receiving Lenalidomide Maintenance.

Guidelines recommend vaccination starting 12 months after autologous hematopoietic stem cell transplant (aHCT), but there is varying practice for patients on maintenance therapy, with some centers not immunizing at all. Because of decreased vaccine rates among the general population causing loss of herd immunity, we aimed to establish the safety and efficacy of revaccinating multiple myeloma patients on lenalidomide maintenance (LM). Of the 122 patients who were vaccinated after aHCT between 2010 and 2014 at Memorial Sloan Kettering Cancer Center, 91 (75%) were on LM.

Impact of Toxicity on Survival for Older Adult Patients after CD34 Selected Allogeneic Hematopoietic Stem Cell Transplantation.

Ex vivo CD34 selection before allogeneic hematopoietic stem cell transplantation (allo-HCT) reduces graft-versus-host disease without increasing relapse but usually requires myeloablative conditioning. We aimed to identify toxicity patterns in older patients and the association with overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of 200 patients who underwent CD34 selection allo-HCT using the ClinicMACS® system between 2006 and 2012.

Effects of Late Toxicities on Outcomes in Long-Term Survivors of Ex-Vivo CD34-Selected Allogeneic Hematopoietic Cell Transplantation.

The late adverse events in long-term survivors after myeloablative-conditioned allogeneic hematopoietic cell transplantation (HCT) with ex vivo CD34 cell selection are not well characterized. Using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0, we assessed all grade ≥3 toxicities from the start of conditioning to the date of death, relapse, or last contact in 131 patients who survived >1 year post-HCT, identifying 285 individual toxicities among 17 organ-based toxicity groups.

Diagnosis of Extrapulmonary Legionellosis in Allogeneic Hematopoietic Cell Transplant Recipients by Direct 16S Ribosomal Ribonucleic Acid Sequencing and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.

Identifying extrapulmonary legionellosis is difficult due to the lack of clinical suspicion and limitations of conventional microbiologic methods. We present a case series of hematopoietic cell transplant recipients with extrapulmonary legionellosis diagnosed via molecular diagnostics: 16S ribosomal ribonucleic acid gene Sanger sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

T Cell Depletion as an Alternative Approach for Patients 55 Years or Older Undergoing Allogeneic Stem Cell Transplantation as Curative Therapy for Hematologic Malignancies.

T cell-depleted (TCD) allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for hematologic malignancies in adults, shown to reduce graft-versus-host disease (GVHD) without increased relapse. We retrospectively reviewed a single-center, 11-year experience of 214 patients aged ≥ 55 years to determine tolerability and efficacy in the older adult. Most patients (70%) had myeloid diseases, and most acute leukemias were in remission.

The Impact of Toxicities on First-Year Outcomes after Ex Vivo CD34-Selected Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies.

Factors that impact first-year morbidity and mortality in adults undergoing myeloablative allogeneic hematopoietic cell transplantation with ex vivo CD34 selection have not been previously reported. We assessed all toxicities ≥ grade 3 from the start of conditioning to date of death, relapse, or last contact in 200 patients during the first year after transplantation, identifying 1885 individual toxicities among 17 organ-based toxicity groups. The most prevalent toxicities in the first year were of infectious, metabolic, hematologic, oral/gastrointestinal, hepatic, cardiac, and pulmonary etiologies.

A Chemotherapy-Only Regimen of Busulfan, Melphalan, and Fludarabine, and Rabbit Antithymocyte Globulin Followed by Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplantations for the Treatment of Myeloid Malignancies.

We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplantations (HSCT) without the need for total body irradiation, thereby reducing toxicity while maintaining low rates of graft-versus-host disease (GVHD) and without increasing relapse. We investigated the myeloablative combination of busulfan (Bu) and melphalan (Mel), with the immunosuppressive agents fludarabine (Flu) and rabbit antithymocyte globulin (r-ATG) as cytoreduction before a TCD HSCT. No post-transplantation immunosuppression was administered.

Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation.

We aimed to identify whether the use of autologous hematopoietic cell transplantation (HCT) impacts outcomes for multiple myeloma patients with gains of chromosome 1q (+1q). We retrospectively identified 95 patients, 21% having +1q. For patients with +1q, the overall response rate to induction was 85%, with 40% having ≥ VGPR and 20% achieving a CR, similar to non +1q patients (p = .

Ex Vivo CD34-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response.

Ex vivo CD34-selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34-selected TCD allo-HSCT without post-HCST immunosuppression in a single institution.

Hematopoietic Cell Transplantation Comorbidity Index Predicts Outcomes in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Receiving CD34 Selected Grafts for Allogeneic Hematopoietic Cell Transplantation.

To evaluate the association between the hematopoietic cell transplantation-comorbidity index (HCT-CI) and the recently developed age-adjusted HCT-CI (HCT-CI/age) and transplant outcomes in the setting of CD34-selected allogeneic HCT, we analyzed a homogeneous population of patients undergoing allogeneic HCT with CD34-selected grafts for acute myeloid leukemia and myelodysplastic syndrome (n = 346). Median HCT-CI and HCT-CI/age scores were 2 (percentile 25 to 75, 1 to 4) and 3 (percentile 25 to 75, 1 to 5), respectively. Higher HCT-CI and HCT-CI/age scores were associated with higher nonrelapse mortality (NRM) and lower overall survival (OS).

Upfront use of plerixafor and granulocyte-colony stimulating factor (GCSF) for stem cell mobilization in patients with multiple myeloma: efficacy and analysis of risk factors associated with poor stem cell collection efficiency.

Plerixafor (P), an agent that selectively and reversibly binds to the chemokine receptor CXCR4, has been approved in combination with G-CSF (P + G-CSF) for stem cell (SC) mobilization in patients with multiple myeloma (MM). The goal of this study was to determine the SC collection success rate of P + G-CSF using a clinically relevant outcome defined as the ability to collect at least 5 × 10 CD34 cells/kg to allow safely two transplants, and identify risk factors impacting SC mobilization. One hundred and thirty-eight patients were mobilized with P + G-CSF upfront following induction.