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Results for “relapsed myeloma”

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PubMed1976

Doxorubicin/B.C.N.U. chemotherapy for multiple myeloma in relapse.

A combination of doxorubicin ('Adriamycin") and B.C.N.U. (1,3 di[2-chloroethyl]-1-nitrosourea) (30 mg/m2 of each intravenously every 3-4 weeks) was used to treat thirteen multiple-myeloma patients who did not respond or were in relapse after remission produced by alkylating-agent/prednisone therapy. All cases were staged according to total-body myeloma-cell number and followed quantitatively for response to therapy. Seven of the thirteen patients responded (54%). Two had complete clinical remissions and a greater than 75% reduction in tumour-cell mass lasting 12 and 16 months. Five others had partial remissions with lesser degrees of tumour-mass reduction and bone pain and improved haemoglobin and serum-albumin concentrations. Toxicity was limited to occasional myelo-suppression, mild alopecia, and nausea. The results indicate the usefulness of doxorubicin/B.C.N.U. for myeloma patients who have relapsed during previously effective alkylating-agent therapy.

Alkylating Agents↗

PubMed2026

Gut Microbiome Composition Is Associated With Response to CD38 Antibody (Daratumumab) Treatment Among Relapsed Multiple Myeloma Patients.

INTRODUCTION: Growing data support interactions between host-gut microbes and treatment responses in multiple myeloma (MM), where a higher abundance of Eubacterium hallii in stool samples has been found among MM patients with negative minimal residual disease after induction therapy. Here, we evaluated changes in the gut microbiome associated with daratumumab (dara) based therapy in 40 MM patients, before and after therapy. PATIENTS AND METHODS: Patients with relapsed MM and prior autologous transplantation who had received 1 to 4 prior lines of therapy were eligible. Two stool samples were collected, one within 1 week prior to dara (predara) and one immediately after 4 doses of dara (postdara). Metagenomics sequencing was conducted. Microbiome taxonomic analyses were performed using MetaPhlAn4, and microbial functional pathway analyses were conducted using HUMAnN3.6. QIIME2 was used for compositional and statistical analyses. RESULTS: Of 40 participants enrolled, there were 5 nonresponders; 35 patients achieved partial response (PR) or better (responders). Among responders, 10 patients achieved complete remission (CR), and 25 patients achieved either very good partial response (VGPR) or PR. There were no statistically significant differences between overall pre and postdara gut microbiomes. Differential abundance analysis (ANCOM-BC) showed statistically significant (q ≤ 0.05) overgrowth of Alistipes finegoldii and Acidaminococcus intestini species in responders and Ruminococcus torques, Sellimonas intestinalis and Clostridium symbiosum in nonresponders. Compared to non-CR, CR samples showed enrichment of Faecalibacterium prausnitzii; non-CR samples were enriched in Segatella copri and Faecalimonas umbilicata. DISCUSSION/CONCLUSION: Our results suggest differences in species between clinical responders and nonresponders, but larger prospective studies are needed to confirm these results.

Clinical response↗

PubMedDate not supplied

[Multiple myeloma and acute leukemia. Simultaneous evolution of plasmacyte and myelomonocytic clones].

The authors report two cases of acute myelo-monocytic leukemia occuring during the course of multiple myeloma treated by local radiotherapy and melphalan. Both patients underwent a complete remission of their myeloma for 27 and 78 months. The myeloma relapsed suddenly in the form of an acute leukemia. In one case, the onset of acute leukemia was preceded by a syndrome of marrow failure with numerous crown-shaped sideroblasts and an excess of myeloblasts in the marrow. This stage lasted two years. The biochemical abnormalities of the red cells usually associated with refractory anemia and preleukemic conditions were present in the other case.

Aged↗

PubMed1979

Interferon therapy in multiple myeloma.

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.

Aged↗

PubMed1978

Relapsing annular erythema and myeloma successfully treated with cyclophosphamide.

We report the history of a patient, who had recurrent patches of erythema on the trunk and extremities for some years. The diagnosis of erythema elevatum diutinum or annulare centrifugum was discussed. The patient developed a monoclonal IgA lambda fraction and clinical signs of myeloma. Treatment with cyclophosphamide stopped the development of erythema and also caused the M-component to disappear. This improvement has persisted even without cytostatic treatment. Another patient with prostatic carcinoma and relapsing annular erythema was cured of his skin lesions, when his carcinoma was treated with estrogens. The literature is reviewed.

Aged↗

PubMed2026

Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial.

Teclistamab, a B cell maturation antigen-targeting bispecific antibody, has demonstrated substantial activity in relapsed multiple myeloma (MM), particularly in earlier lines of therapy, and may have higher efficacy in high-risk smoldering MM (HR-SMM) with a more functional immune system. In the randomized phase 2 ImmunoPRISM trial, we compared fixed-duration teclistamab with lenalidomide-dexamethasone (Rd) in HR-SMM. After a six-patient safety run-in, patients were randomized 2:1 to teclistamab or Rd. The primary endpoint was complete response (CR) rate. As of 26 May 2026, 59 patients were treated-45 received teclistamab and 14 received Rd. Teclistamab treatment induced a CR in 77.8% patients versus 0% with Rd, and minimal residual disease negativity at 10-5 in 82.2% patients. At a median follow-up of 24.5 months, 2-year progression-free survival was 92% with teclistamab versus 49% with Rd. Overall, response rates, duration of response and time to progression (TTP) were significantly improved in teclistamab compared to Rd. Toxicities in the teclistamab arm included grades 1-2 cytokine release syndrome, no neurotoxicity and no increase in grade 3 infections compared to Rd (20% versus 21%). No deaths occurred in either arm. Teclistamab represents a highly active immune-interception strategy for HR-SMM. ClinicalTrials.gov registration: NCT05469893 .

Journal Article↗

PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART↗

PubMed2026

Prolonged Cytopenia After Idecabtagene Vicleucel for Multiple Myeloma is Associated with Poor Overall Survival.

Cytopenias are well-recognized toxicities of idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T cell (CAR-T) therapy approved for the treatment of relapsed, refractory multiple myeloma (RRMM). However, little is known of prognostic implications of cytopenias that persist 30 to 100 days after CAR-T infusion. We report the duration, incidence, and impact on outcomes of post-CAR-T cytopenias at Day 30 and Day 100, defined as an absolute neutrophil count of <500 cells/mm3 and/or platelet count <20 × 109 cells/L, per the recent definitions of immune effector cell-associated hematotoxicity for neutropenia (N-ICAHT) and thrombocytopenia (T-ICAHT). Using observational data from the Center for International Blood and Marrow Transplant Research, we identified 821 patients treated during 2021 to 2023. The cumulative incidence of cytopenias at Day 30 was 25% and at Day 100 was 2%. Patients with Day 30 cytopenias had inferior progression-free survival (PFS) (39% versus 45%, P = .01) and overall survival (OS) at 12 months (57% versus 76%, P < .01). While there was no significant difference in PFS in patients who had Day 100 cytopenias (42% versus 53%, P = .12), compared to those who did not, patients with Day 100 cytopenias had significantly inferior OS at 12 months (55% versus 82%, P < .01). High (≥2) chimeric antigen receptor cell-mediated hematotoxicity score was associated with cytopenias at Day 30 (hazard ratio 5.26, P < .001). Cytopenias at Day 30 after ide-cel were associated with inferior PFS and OS. In addition, cytopenias at Day 100 after ide-cel are rare and are associated with inferior OS.

CAR-T↗

PubMed2026

A novel triple-knockout allogeneic BCMA CAR T-cell therapy (CT0590) for multiple myeloma: preclinical and phase 1 study.

Host-versus-graft reaction (HVGR) is a major challenge in allogeneic chimeric antigen receptor (CAR) T-cell therapy. To counter host natural killer (NK) cell attacks, we armored allogeneic, HLA-I-deficient, B-cell maturation antigen (BCMA)-targeting CAR T cells with an NKG2A CAR. In vitro and animal studies demonstrated that allogeneic CAR-NKG2A T cells effectively resisted host NK cell-mediated killing. BCMA and NKG2A dual-targeting allogeneic CAR T cells (CT0590) resisted killing by NK cells and showed robust antitumor activity in preclinical in vivo models. On the basis of these data, a first-in-human study enrolled 5 patients (4 with relapsed and refractory multiple myeloma [RRMM] and 1 with primary plasma cell leukemia [pPCL]). CT0590 was well tolerated and caused no dose-limiting toxicities, treatment-related death, or graft-versus-host disease. Three patients achieved confirmed responses, including 2 with stringent complete response (sCR). Notably, sCR in the patient with RRMM was still ongoing (duration of response >23 months) at the time of data cutoff, and sCR in the patient with pPCL lasted for 20 months. Both patients showed robust expansion of universal CAR T cells (maximum concentration of >280 000 copies per μg genomic DNA) and higher baseline NKG2A expression on NK cells than nonresponders. These results suggest that CAR-NKG2A technology may overcome HVGR, especially in patients with elevated NKG2A expression on NK cells. Further studies of CT0590 in RRMM and pPCL are warranted. This trial was registered at www.clinicaltrials.gov as NCT05066022.

Humans↗

PubMed2026

Daratumumab monotherapy for relapsed AL amyloidosis: a single center retrospective analysis.

PURPOSE: Treatment of relapsed AL amyloidosis remains challenging as patients frequently suffer from severe organ dysfunctions. Daratumumab, a cornerstone drug in multiple myeloma and newly diagnosed AL amyloidosis, has also shown promise in relapsed AL amyloidosis. MATERIALS AND METHODS: To assess the efficacy of daratumumab, we conducted a retrospective study of 40 patients who received daratumumab monotherapy in our prospective amyloidosis cohort. RESULTS: The median age of the cohort was 67 years, and 31 patients were classified as stage III/IV by the Mayo 2012 guidelines and 32 patients as stage IIIa/IIIb by the European staging system. The overall hematologic and cardiac response rates were 72.5% and 42.4%, respectively. With median follow-up duration of 26.9 months, the estimated median progression-free survival was 21.9 months. Deep hematologic (p < 0.001) and cardiac response (p = 0.001) were associated with prolonged progression free survival. The duration of hematologic/cardiac responses were 26.2 months and 27.8 months, respectively. The median overall survival was 30.9 months. Treatment was well tolerated, as with 3 patients experiencing grade 3-4 hematologic adverse events and 8 experiencing grade 3-4 non-hematologic adverse events. DISCUSSION: Our findings suggest that daratumumab monotherapy provides rapid and durable responses and is generally well tolerated in patients with relapsed AL amyloidosis.

AL amyloidosis↗

PubMed2025

Mutagenic Impact and Evolutionary Influence of Chemoradiotherapy in Hematologic Malignancies.

UNLABELLED: Ionizing radiotherapy (RT) is a widely used treatment strategy for malignancies. In solid tumors, RT-induced double-strand breaks lead to the accumulation of insertion-deletions (indels; ID), and their repair by nonhomologous end joining has been linked to the ID8 mutational signature in surviving cells. However, the extent of RT-induced mutagenesis in hematologic malignancies and its impact on their mutational profiles and interplay with commonly used chemotherapies has not yet been explored. In this study, we interrogated 580 whole-genome sequence (WGS) samples from patients with large B-cell lymphoma, multiple myeloma, and myeloid neoplasms and identified ID8 only in relapsed disease. Yet ID8 was detected after exposure to both RT and mutagenic chemotherapy (i.e., platinum and melphalan). Using WGS of single-cell colonies derived from treated lymphoma cells, we revealed a dose-response relationship between RT and platinum and ID8. Finally, using ID8 as a genomic barcode, we demonstrate that a single RT-surviving cell may seed distant relapse. SIGNIFICANCE: RT and the ID8 indel signature are related, but their genomic impact on hematologic malignancies is unclear. Leveraging WGS, we linked ID8 to both RT and mutagenic chemotherapy and validated that platinum can induce ID8. We used ID8 as a genomic barcode to reveal that RT-resistant cells may seed systemic relapse.

Humans↗

PubMed1977

Phase II study of oral methyl-CCNU and prednisone in previously treated alkylating agent-resistant multiple myeloma.

Thirteen patients with multiple myeloma (MM) who either failed to respond to or who were relapsing from standard agents and who received four or more courses of methyl-CCNU + prednisone (adequate drug trial) are reported in this paper. Methyl-CCNU was given orally before breakfast at 6-week intervals at a starting dose of 50 mg/m2 with the intention of increasing the dose to 100, 150, and 200 mg/m2 with each subsequent course. The dose of prednisone was 75 mg/day x 7 with each course. The response rate was 46% (six of 13 patients). No patient had better than a fair response. Drug toxicity, severe enough to prevent further dose escalation, was observed in every case. Prior BCNU therapy or the lack of response to previous alkylating agents did not prevent a response to methyl-CCNU + prednisone. The response rate of methyl-CCNU + prednisone in MM is comparable to the results achieved with other agents in similar groups of patients.

Administration, Oral↗

PubMed2026

Integrated Genomic and Epigenomic Analysis Reveals Epigenetic Plasticity in Disease Progression and Multidrug Resistance in Multiple Myeloma.

UNLABELLED: Multiple myeloma is marked by recurrent cytogenetic abnormalities and mutations that accumulate as the disease progresses. In this study, we sought to elucidate the transitions driving tumorigenesis and therapy resistance in multiple myeloma using a unique cohort of nearly 900 patients spanning premalignant to late-stage refractory multiple myeloma, comprehensively characterized at molecular and clinical levels. Waves of epigenetic dysregulation drove these critical transitions. In this paradigm, genomic and cytogenetic events unlocked epigenetic plasticity, reshaping multiple myeloma cell biology to evade tumor microenvironment constraints and therapeutic pressures. Functional perturbation studies in an isogenic proteasome inhibitor-resistant cell line model demonstrated enhanced reliance on transcriptional cofactors, supporting a mechanistic link between chromatin plasticity and therapy adaptation. Collectively, these findings support a unifying framework in which genomic heterogeneity unlocks gene regulatory plasticity, enabling plasma cells (PC) to evade microenvironmental constraints and therapeutic pressure. These results provide a mechanistic explanation for sequential relapse without new genomic alterations and nominate epigenetic plasticity-mediated PC adaptation as a therapeutic vulnerability in the heterogeneous genetic background of multiple myeloma. SIGNIFICANCE: Assembly and analysis of a multiple myeloma cohort spanning the continuum from premalignant to late relapse that integrates bulk transcriptomics with single-cell multiomic data provides insights into disease progression and epigenetic plasticity.

Multiple Myeloma↗

PubMed2025

Biallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma.

Monoclonal antibodies targeting CD38 are a therapeutic mainstay in multiple myeloma (MM). Although they have contributed to improved outcomes, most patients still experience disease relapse, and little is known about tumor-intrinsic mechanisms of resistance to these drugs. Antigen escape has been implicated as a mechanism of tumor-cell evasion in immunotherapy. Yet, it is unknown whether MM cells can develop permanent resistance to anti-CD38 antibodies by acquiring genomic events leading to biallelic disruption of the CD38 gene locus. Here, we analyzed whole-genome and whole-exome sequencing data from patients 701 newly diagnosed MM, 67 patients at relapse with naivety to anti-CD38 antibodies, and 50 patients collected at relapse after anti-CD38 antibodies. We report a loss of CD38 in 10 of 50 patients (20%) after CD38 therapy, 3 of whom exhibited a loss of both copies. Two of these cases showed convergent evolution in which distinct subclones independently acquired similar advantageous variants. Functional studies on missense mutations involved in biallelic CD38 events revealed that 2 variants, L153H and C275Y, decreased binding affinity and antibody-dependent cellular cytotoxicity of the commercial antibodies daratumumab and isatuximab. However, a third mutation, R140G, conferred selective resistance to daratumumab, while retaining sensitivity to isatuximab. Clinically, patients with MM are often rechallenged with CD38 antibodies after disease progression and these data suggest that next-generation sequencing may play a role in subsequent treatment selection for a subset of patients.

Humans↗

PubMed1978

Unmaintained remissions in multiple myeloma.

Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

Cell Transformation, Neoplastic↗

PubMed1979

The chemotherapy of plasma-cell myeloma and the incidence of acute leukemia.

Previously untreated patients with myeloma were randomized to initial treatment with melphalan and prednisone (and to cyclophosphamide or carmustine if relapse or progression occurred)(Group A, 125 patients), melphalan, cyclophosphamide, carmustine and prednisone in alternating (Group B, 123 patients) or concurrent (Group C, 116 patients) schedules. The groups were similar with respect to known prognostic factors. Response rates and survival were also similar. We were unable to identify a subgroup of patients who responded or survived better on melphalan-cyclophosphamide-carmustine and prednisone than on melphalan and prednisone. We conclude that the combination of the four drugs is not better than melphalen and prednisone for inducing responses or prolonging the survival of patients with myeloma. Myelomas producing only gamma chains have a poorer prognosis (P greater than 0.001) than IgG, IgA, or kappa myeloma. Acute leukemia has developed in 14 patients. The actuarial risk of developing acute leukemia, has increased rapidly to 17.4 per cent at 50 months.

Acute Disease↗

PubMed1977

Primary bioassay of human myeloma stem cells.

The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 10(5)-10(6) and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B)-cell neoplasia. In addition, systematic and predictive studies of anticancer drug effects on myeloma stem cells should now be feasible.

Antigen-Antibody Reactions↗

PubMed1977

Ultrastructural and immunocytochemical characterization of circulating mononuclear cells in patients with myelomatosis.

The ultrastructure of blood mononuclear cells from two IgG myeloma patients was studied, and cells reacting with anti-idiotypic serum and polyspecific anti-Ig serum were characterized by immunoperoxidase techniques. Abnormal, mononuclear cells were present in the blood of both patients, which morphologically were classified as atypical small to medium-sized lymphocytes, polymorphic immature lymphocytes (lymphoblasts), predominantly of the lymphoplasmocytic type and atypical, plasmocytic cells or myeloma cells. Immunocytochemical observations showed that most of the abnormal cells, including atypical small to medium-sized lymphocytes, reacted with anti-idiotypic and polyspecific anti-Ig serum. Periods of relapse and remission were correlated with an increase and decrease, respectively, of the number of abnormal cells and cells which reacted with anti-idiotype and anti-Ig serum. The observations indicate that circulating lymphoid cells are part of the myeloma clone.

Fluorescent Antibody Technique↗