bims-hemali 2024-12-01 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2024–12–01
seventeen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Isatuximab for Stem Cell Transplant-Ineligible Multiple Myeloma: An Editorial.
BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma.
Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients Aged over 65 Years: A Propensity Score-Matched Study.
A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.
Local Cytokine Release Syndrome After Idecabtagene Vicleucel Therapy in Patients With Multiple Myeloma: Two Case Reports.
Efficacy and safety of the combination of decitabine and CHAG priming regimen in the relapsed or refractory acute myeloid leukemia.
Historical Perspective of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.
Survival trends using DPd vs. other triplets in early RRMM patients: a population-adjusted indirect treatment comparison.
Optimizing treatment sequencing in multiple myeloma: a novel model to predict survival outcomes.
Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future Directions.
Smoldering multiple myeloma: Integrating biology and risk into management.
Change in hair texture with the use of pomalidomide for multiple myeloma: From straight to curly phenotype.
Venetoclax plus D-CAG (decitabine, cytarabine, aclarubicin, G-CSF) for elderly or unfit patients with newly diagnosed acute myeloid leukemia: a multicenter, prospective study.
Outcomes with loncastuximab tesirine following CAR T-cell therapy in patients with relapsed or refractory diffuse large B-cell lymphoma.
Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM).
Combining azole antifungals with venetoclax plus azacitidine in patients with newly diagnosed acute myeloid leukemia.
Characteristics and Treatment Patterns of Long-surviving Patients With Multiple Myeloma: Over 13 Years of Follow-up in the ConnectⓇ MM Registry.

Cureus. 2024 Oct;16(10): e72177

Isatuximab for Stem Cell Transplant-Ineligible Multiple Myeloma: An Editorial.

Abdul Haseeb Hasan, Muhammad Ali Abid, Bisma Tariq.

  The recent approval of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (Isa-VRd) marks a significant advancement in the treatment of stem cell transplant-ineligible multiple myeloma (MM) patients. MM, the second most common hematological malignancy globally, poses substantial challenges, especially for patients who are unable to undergo autologous stem cell transplantation due to advanced age or comorbidities. Isatuximab, a CD38-targeting monoclonal antibody, has demonstrated promising efficacy in the pivotal trial, which reported a 40% reduction in disease progression or death for patients treated with Isa-VRd compared to bortezomib-lenalidomide-dexamethasone alone. The trial also showed higher rates of complete response and minimal residual disease (MRD)-negative status in the Isa-VRd group without introducing new safety concerns. These findings suggest that isatuximab's integration into first-line therapy could substantially improve long-term outcomes for this underserved patient population. Clinicians are encouraged to adopt regular MRD monitoring and provide comprehensive patient education on potential side effects to optimize treatment adherence. Further research on isatuximab's use in combination with other emerging therapies may continue to expand therapeutic possibilities, offering hope for more effective management of MM.

Keywords:  bortezomib; cd38; dexamethasone; fda; imroz; isatuximab; lenalidomide; monoclonal antibody; multiple myeloma

DOI:  https://doi.org/10.7759/cureus.72177
J Transl Med. 2024 Nov 29. 22(1): 1087

BCMA CAR-T therapy combined with pomalidomide is a safe and effective treatment for relapsed/refractory multiple myeloma.

Yuhan Yan, Yixuan Tu, Qian Cheng, Jian Zhang, Erhua Wang, Zuqun Deng, Yan Yu, Liwen Wang, Rui Liu, Ling Chu, Liqing Kang, Jing Liu, Xin Li.

   BACKGROUND: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy.
METHODS: We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro.
RESULTS: The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1-14) months, while the OS (overall survival) was 10.7 (1.2-16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7-13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity.
CONCLUSIONS: Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM.

Keywords:  BCMA CAR T-cell therapy; Combination therapy; Pomalidomide; Relapsed/Refractory multiple myeloma (R/R MM)

DOI:  https://doi.org/10.1186/s12967-024-05772-w
Hematol Rep. 2024 Nov 18. 16(4): 714-723

Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients Aged over 65 Years: A Propensity Score-Matched Study.

Satoshi Yamasaki, Michitoshi Hashiguchi, Nao Yoshida-Sakai, Hiroto Jojima, Koichi Osaki, Takashi Okamura, Yutaka Imamura.

   BACKGROUND: The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging.
METHODS: We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023.
RESULTS: Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (i.e., those previously treated with daratumumab and receiving isatuximab plus pomalidomide and low-dose dexamethasone because of disease progression during treatment with daratumumab [n = 6], daratumumab plus pomalidomide and low-dose dexamethasone [n = 9], or isatuximab plus pomalidomide and low-dose dexamethasone without daratumumab-exposure [n = 14]) than in the anti-CD38 mAb-naïve group (no exposure to daratumumab or isatuximab [n = 49]) (p < 0.001). To address potential confounder factors associated with use or nonuse of anti-CD38 mAbs, we performed propensity score matching (PSM) using age, sex, performance status, and Geriatric 8 and Instrumental Activities of Daily Living scores. PSM identified 14 subjects from the anti-CD38 mAb-exposed group with baseline characteristics similar to those of 14 subjects from the anti-CD38 mAb-naïve group. After PSM, the adjusted OS was significantly longer in the anti-CD38 mAb-exposed group than in the anti-CD38 mAb-naïve group (p < 0.001).
CONCLUSION: These findings provide insights into the optimal use of anti-CD38 mAbs in patients with RRMM who are transplant-ineligible and aged ≥65 years and on candidates who are appropriate for novel approaches, such as chimeric antigen receptor T-cell or bispecific T-cell engager therapy.

Keywords:  daratumumab; isatuximab; multiple myeloma; older patients; propensity score matching analysis; relapsed or refractory

DOI:  https://doi.org/10.3390/hematolrep16040068
Int J Hematol. 2024 Nov 28.

A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.

Tadao Ishida, Yoshiaki Kuroda, Kosei Matsue, Takuya Komeno, Takuro Ishiguro, Jun Ishikawa, Toshiro Ito, Hiroshi Kosugi, Kazutaka Sunami, Kazuko Nishikawa, Kazuhiro Shibayama, Kensuke Aida, Hiroshi Yamazaki, Mitsuo Inagaki, Hisanori Kobayashi, Shinsuke Iida.

  We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2. In phase 1, 14 patients received once-weekly (QW) subcutaneous teclistamab (0.72 mg/kg [n = 5]; 1.5 mg/kg [n = 5]; 3 mg/kg [n = 4]). No dose-limiting toxicities were observed. As of April 2024, 26 phase-2 patients received the recommended phase-2 dose (QW) (RP2D: 1.5 mg/kg) of teclistamab. Biweekly (Q2W) dosing was allowed after maintaining response for ≥ 6 months. At a median follow-up of 14.32 months, ORR was 76.9% (≥ very good PR: 76.9%; ≥ complete response: 65.4%). Median duration of response, progression-free survival, and overall survival were not reached. Common TEAEs included CRS (grade ≤ 2), neutropenia, and infections. No patient had immune effector cell-associated neurotoxicity syndrome (ICANS) and dose reductions. Teclistamab demonstrated deep and durable responses in Japanese patients with RRMM, consistent with the global pivotal MajesTEC-1 study, supporting the potential for a new standard of care for Japanese RRMM patients.

Keywords:  B-cell maturation antigen; Bispecific antibody; Japanese; Multiple myeloma; Teclistamab

DOI:  https://doi.org/10.1007/s12185-024-03884-z
Cureus. 2024 Oct;16(10): e72364

Local Cytokine Release Syndrome After Idecabtagene Vicleucel Therapy in Patients With Multiple Myeloma: Two Case Reports.

Taku Kikuchi, Nobuhiro Tsukada, Kodai Kunisada, Moe Nomura-Yogo, Tadao Ishida.

  Chimeric antigen receptor T-cell (CAR-T) therapy targeting the B-cell maturation antigen (BCMA) is an effective treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, cytokine release syndrome (CRS) represents a significant complication associated with CAR-T therapy. While most CRS cases involve systemic symptoms such as fever, hypotension, and respiratory distress, localized symptoms (referred to as local CRS) can also occur. Herein, we report two cases of local CRS without cervical lesions that occurred at our institution. Both patients had triple-class refractory RRMM prior to therapy. Following idecabtagene vicleucel (ide-cel) administration, both developed grade 1 CRS on the day of ide-cel administration; one case improved with tocilizumab, while the other improved with tocilizumab and dexamethasone (dex). However, on the third day post-administration, they exhibited symptoms characterized by neck swelling, leading to a risk of airway obstruction. Both cases were diagnosed as local CRS, and prompt dex administration resulted in rapid symptom improvement. These cases underscore the importance of monitoring for local CRS even in the absence of "cervical myeloma lesions", particularly during the early phase following ide-cel administration. Early administration of dex is crucial for the effective management of local CRS.

Keywords:  cervical edema; chimeric antigen receptor-t cell; dexamethasone; local cytokine release syndrome; multiple myeloma

DOI:  https://doi.org/10.7759/cureus.72364
Sci Rep. 2024 11 25. 14(1): 29161

Efficacy and safety of the combination of decitabine and CHAG priming regimen in the relapsed or refractory acute myeloid leukemia.

Yan Wu, Jinping Liang, Ruihua Mi, Lin Wang, Lin Chen, Xudong Wei.

  Efficacy and safety analysis of the combination of decitabine priming followed by CHAG chemotherapy in treatment of relapsed/refractory(r/r) acute myeloid leukemia (AML). Between January 2013 and June 2020, 62 r/r AML patients in our center receiving therapy including combination of decitabine and CHAG pre-excitation regimen were enrolled. Primary objectives were overall response (ORR: complete remission + partial remission), adverse events, overall survival (OS) and relapse-free survival (RFS). There were 46 patients (74.2%) with complete remission (CR), 5 patients (8.06%) with partial remission (PR), ORR was 82.2%. Main adverse events were bone marrow suppression, fever and infection, and no chemotherapy-related deaths occurred. The median RFS time was 4.3 months (0.3 ~ 65 months), and median OS time was 7.75 months (1 ~ 66.3 months). Decitabine priming followed by CHAG regimen is effective and tolerated in patients with r/r AML, and can be used as a salvage treatment for patients with r/r AML.

Keywords:  Acute; Decitabine; Leukemia; Myeloid; Pre-excitation regimen; Relapsed or refractory

DOI:  https://doi.org/10.1038/s41598-024-80496-x
Acta Haematol. 2024 Nov 25. 1-21

Historical Perspective of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Muhammad Faisal Aslam, Asfand Yar Cheema, Daniyal Shahid, Bibi Maryam, Debduti Mukhopadhyay, Mishaal Munir, Ali Najam, Hossam M Ali, Qaiser Bashir, Faiz Anwer.

BACKGROUND: Advances in novel therapies have improved outcomes for multiple myeloma (MM) patients and the use of allo-SCT has decreased. Current guidelines no longer support allo-SCT as consolidation therapy for newly diagnosed MM, even in high-risk cases.
SUMMARY: Allo-SCT is now typically considered only within clinical trials for young, high-risk patients with relapsed or refractory MM (RRMM). It has not proven favorable despite its historical use. CAR T-cell therapy and bispecific antibodies have shown promise in treating triple- and penta-exposed/refractory MM, yet relapse remains common with poor survival rates. The efficacy of allo-SCT following BCMA-directed therapy and other new T-cell-directed therapies is unclear. Allo-SCT might be a viable option for eligible patients who relapse after these therapies, or where such options are unavailable. Advancements in reduced-intensity conditioning regimens have led to lower toxicity and transplant-related (TR) morbidity, lower graft versus host disease (GVHD) and TR mortality. Expanded use of alternative donors, like haploidentical donors, has yielded comparable outcomes. Better post-transplant GVHD regimens and maintenance strategies to prevent relapse have been developed.
KEY MESSAGES: This review analyzes available literature to better understand the safety, efficacy, and current role of allo-SCT in managing MM. Newer regimens are needed as routine use of allo-SCT cannot be recommended.

DOI: https://doi.org/10.1159/000542704
Future Oncol. 2024 Nov 29. 1-10

Survival trends using DPd vs. other triplets in early RRMM patients: a population-adjusted indirect treatment comparison.

Faiz Anwer, Tommy Lan, Michael Dolph, Hoora Moradian, Samantha Slaff, Yu-Hsuan Shih, Derek Tang.

   AIMS: Limited head-to-head data exist for daratumumab plus pomalidomide and dexamethasone (DPd) and non-pomalidomide-containing triplet regimens to treat relapsed/refractory multiple myeloma (RRMM). This study conducted population-adjusted indirect comparisons of overall survival (OS) for DPd vs. daratumumab, carfilzomib, and dexamethasone (DKd) and daratumumab, bortezomib, and dexamethasone (DVd).
MATERIALS & METHODS: A systematic literature review was performed via searches of databases and relevant conference proceedings. Both simulated treatment comparison (STC) and matching-adjusted indirect comparison (MAIC) were used to adjust for between-trial differences.
RESULTS: Seven randomized controlled trials were identified, five of which were subsequently excluded from the indirect treatment comparison during feasibility assessment. A consistent OS benefit was observed for DPd vs. DKd and DVd for patients with RRMM, using both STC and MAIC methods.
CONCLUSIONS: The findings of this study support the use of DPd over DKd and DVd for the treatment of patients with early RRMM.

Keywords:  Daratumumab plus pomalidomide and dexamethasone; matching-adjusted indirect comparison; multiple myeloma; overall survival; relapsed/refractory; simulated treatment comparison; triplet regimens

DOI:  https://doi.org/10.1080/14796694.2024.2426443
Hematology. 2024 Dec;29(1): 2432815

Optimizing treatment sequencing in multiple myeloma: a novel model to predict survival outcomes.

Maria Teresa Petrucci, Sara Bringhen, Cristina Entrala Cerezo, João Mendes, Patrizio Armeni.

   OBJECTIVE: Patients with multiple myeloma (MM) typically require multiple regimens and become harder to treat with each line of treatment. Furthermore, there is a lack of direct comparative clinical trial data to guide effective treatment sequencing. A novel model is described comparing alternative MM treatment sequences to optimize patient outcomes.
METHODS: The model compares treatment sequences and outcomes for adults with newly diagnosed transplant-eligible (TE) or transplant-ineligible (TIE) MM across four treatment lines (first-line [FL] to fourth-line [4L]). Inputs are derived from patient-level data from clinical trials and indirect treatment comparisons. We report a base case prediction using data representing clinical practice in Italy.
RESULTS: For FL TE, overall survival (OS) and progression-free survival (PFS) were greatest for FL regimens containing daratumumab; OS ranged from 11.80-18.10 years. PFS ranged from 4.82-13.42 years (FL) to 0.66-6.03 years (second-line [2L]), 0.81-1.76 years (third-line [3L]), and 0.69-0.72 years (4L). For FL TIE, OS rates were greater for treatment sequences with FL daratumumab vs. sequences with either 2L or no daratumumab (OS ranging from 5.95-10.61 years). PFS was greatest for FL daratumumab regimens in the TIE group, with PFS ranging from 2.12-7.48 years (FL), 0.53-4.73 years (2L), 0.63-1.17 years (3L), and 0.42 years (4L).
DISCUSSION: This novel model demonstrates that using the most effective treatment in FL optimizes treatment sequencing and clinical outcomes for patients.
CONCLUSION: The optimal MM treatment sequences begin with daratumumab-containing regimens in FL and improve outcomes compared with alternative sequences.

Keywords:  Multiple myeloma; drug therapy; improved outcomes; optimal sequence; overall survival; progression-free survival; treatment lines; treatment sequencing

DOI:  https://doi.org/10.1080/16078454.2024.2432815
Eur J Haematol. 2024 Nov 27.

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future Directions.

Caterina Labanca, Enrica Antonia Martino, Ernesto Vigna, Antonella Bruzzese, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Noemi Puccio, Antonino Neri, Fortunato Morabito, Massimo Gentile.

  Relapsed and refractory multiple myeloma (RRMM) remains a challenging condition despite advances in immunotherapies. Novel bispecific antibodies (BsAbs), including talquetamab, have shown promising efficacy in heavily pretreated patients, even those with triple- and penta-refractory disease. Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs). Administered following a step-up dosing phase to manage cytokine release syndrome (CRS), talquetamab demonstrated a high overall response rate (ORR) of approximately 70%, including in patients previously treated with T-cell redirecting therapies. Its safety profile is consistent with other BsAbs, with hematologic adverse events such as anemia and neutropenia commonly reported, alongside unique on-target off-tumor toxicities like dysgeusia and skin-related events. Infections were less frequent compared to other BsAbs. The optimal sequencing of talquetamab and other therapies, including CAR-T cell treatments, remains an area of active research, as resistance to anti-BCMA therapies presents ongoing clinical challenges. Current trials are exploring the use of talquetamab in combination therapies, as well as therapeutic strategies post-treating progression. The real-world data further support talquetamab's efficacy, making it a valuable addition to the RRMM treatment landscape.

Keywords:  BsAbs; MM; talquetamab; therapy

DOI:  https://doi.org/10.1111/ejh.14353
Semin Hematol. 2024 Oct 18. pii: S0037-1963(24)00112-4. [Epub ahead of print]

Smoldering multiple myeloma: Integrating biology and risk into management.

Roshani Patel, Elizabeth Hill, Madhav Dhodapkar.

  Smoldering multiple myeloma (SMM) was first described over 40 years ago yet much is still unknown including which patients will ultimately progress to symptomatic multiple myeloma (MM). The genetics of the premalignant clone and the immune microenvironment in which it exists is now well understood to both play a role in disease progression. However, the clinical risk models available to help identify patients at most risk of progression still rely primarily on data reflecting volume of disease rather than underlying biology. While it is of upmost importance to accurately diagnose patients with SMM to avoid over or under treatment, efforts are ongoing to tease out if early intervention is indeed warranted for a subgroup of patients with SMM. This article will review the history and biology of SMM, discuss the utility of existing risk models, and examine the efforts to date which have challenged standard management.

Keywords:  Asymptomatic myeloma; Monoclonal gammopathy of undetermined significance (MGUS); Myeloma precursor conditions; Plasma cell disorders; Smoldering multiple myeloma

DOI:  https://doi.org/10.1053/j.seminhematol.2024.10.002
J Oncol Pharm Pract. 2024 Nov 25. 10781552241299698

Change in hair texture with the use of pomalidomide for multiple myeloma: From straight to curly phenotype.

Annam Zahid, Constantin A Dasanu.

   INTRODUCTION: Pomalidomide is used for treating multiple myeloma in patients who have relapsed after prior treatment with lenalidomide and a proteasome inhibitor. Common side effects include mild cytopenias, and deep vein thrombosis. While papulo-erythematous rash has been described, hair effects are rare with this class of agents.
CASE REPORT: We describe a 56-year-old man who was diagnosed with multiple myeloma type IgD lambda six years prior. He responded very well to initial treatment with bortezomib-lenalidomide-dexamethasone. After two years, he had a recurrence that was treated with daratumumab-pomalidomide-dexamethasone, and he entered a stringent complete response (CR) within six months. Daratumumab was discontinued after twelve months, and he subsequently remained on maintenance therapy with pomalidomide. Three months into the maintenance regimen, he noticed a change in hair texture to curly, which continued to progress. Causality assessment linked this change to pomalidomide use via the Naranjo nomogram questionnaire, by scoring 5.
MANAGEMENT AND OUTCOME: Pomalidomide maintenance therapy was continued without any dose alterations given the excellent clinical outcome. A year later, multiple myeloma remains in stringent complete response. The patient remains with a curly hair phenotype, having fully embraced his new physical appearance.
DISCUSSION/CONCLUSION: We report herein a unique hair texture alteration linked with pomalidomide use, not previously documented in literature. The observed hair texture change, from straight to curly, requires further investigation. Future studies may offer more insights into the mechanisms underlying this rare, yet intriguing side effect.

Keywords:  Multiple myeloma; hair change; pomalidomide

DOI:  https://doi.org/10.1177/10781552241299698
Ann Hematol. 2024 Nov 26.

Venetoclax plus D-CAG (decitabine, cytarabine, aclarubicin, G-CSF) for elderly or unfit patients with newly diagnosed acute myeloid leukemia: a multicenter, prospective study.

Hongbing Ma, Yiwen Du, Jianjun Li, Jin Rao, Yong Guo, YunFan Yang, Duanzhong Zhang, Jia Wang, Yi Liao, Yuping Gong.

  Induction regimens with satisfactory remission rates are limited for patients with acute myeloid leukemia (AML) who are elderly or ineligible for intensive chemotherapy. This study is a single-arm, multicenter, prospective phase I/II study (registered with the Chinese Clinical Trial Registry as ChiCTR 2200059694 on May 8, 2022), aiming to evaluate the efficacy and safety of venetoclax plus decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (VD-CAG) for newly diagnosed AML patients who are elderly or ineligible for intensive chemotherapy. The primary endpoint was composite complete remission (CRc) after 1 cycle of induction chemotherapy. The secondary endpoints were measurable residual disease (MRD) by flow cytometry and adverse events. Forty patients(n = 40) received 1 cycle of the VD-CAG regimen for induction chemotherapy. The median age of the patients was 64 (55-81) years, and 10 patients (25%) had secondary AML. Our results showed that 1 cycle of VD-CAG had a high overall response rate of 97.5% and CRc of 95%, and all 10 patients with secondary AML achieved CRc. Moreover, the patients who achieved CRc had deep remission, with MRD-negativity of 71.1% and 54.2% by flow cytometry and molecular assessment, respectively. In addition, blood cell recovery was quick, with a median time to absolute neutrophil count ≥ 1.0 × 109/L and platelet count ≥ 100 × 109/L at 19 days and 15.5 days, respectively. In conclusion, VD-CAG demonstrates high efficacy as an induction treatment for elderly or unfit patients with newly diagnosed AML, and it could be an alternative upfront therapy for this subpopulation, Trials with large-scale subjects are needed for further validation, especially for secondary AML.

Keywords:  Aclarubicin; Acute myeloid leukemia; Decitabine; Induction chemotherapy; Venetoclax

DOI:  https://doi.org/10.1007/s00277-024-06097-w
Blood Cancer J. 2024 Nov 28. 14(1): 210

Outcomes with loncastuximab tesirine following CAR T-cell therapy in patients with relapsed or refractory diffuse large B-cell lymphoma.

Narendranath Epperla, Melanie Lucero, Tom Bailey, Laura Mirams, Jolenta Cheung, Mona Amet, Gary Milligan, Lei Chen.

The efficacy of loncastuximab tesirine (lonca) following chimeric antigen receptor T-cell therapy (CAR-T) progression/failure is unknown. Hence, we sought to examine real-world use and outcomes of lonca following CAR-T in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the USA. In this retrospective study, we included adults (age ≥ 18 years) with R/R DLBCL who received lonca monotherapy as third- (3 L) or fourth line (4 L) treatment after progressing on second line (2 L) or 3 L CAR-T, respectively. Post-CAR-T lonca outcomes included response rates (overall response rate [ORR] and complete response [CR] rate), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 118 patients were included in the analysis with 95 receiving lonca following 2 L CAR-T (median age:66 years; 61% male) and 23 following 3 L CAR-T (median age:57 years; 43% male). Patients with 2 L CAR-T/3 L lonca had an ORR of 73% (CR rate of 34%). With a median follow-up of 8.5 months following lonca initiation, median DOR, PFS, and OS were not reached. The DOR, PFS, and OS at 12 months were 68%, 77%, and 84%, respectively. Patients with 3 L CAR-T/4 L lonca had an ORR of 78% (CR rate of 17%). With a median follow-up of 13 months following lonca initiation, the median DOR and PFS were 7.6 and 12.0 months, while median OS was not reached. OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings including those who were resistant to or progressed after CAR-T.

DOI: https://doi.org/10.1038/s41408-024-01195-4
Medicina (Kaunas). 2024 Nov 20. pii: 1905. [Epub ahead of print]60(11):

Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM).

Josip Batinić, Barbara Dreta, Goran Rinčić, Antonia Mrdeža, Karla Mišura Jakobac, Delfa Radić Krišto, Milan Vujčić, Mario Piršić, Željko Jonjić, Vlatka Periša, Jasminka Sinčić Petričević, Božena Coha, Hrvoje Holik, Toni Valković, Marija Stanić, Ivan Krečak, Ante Stojanović, Domagoj Sajfert, Sandra Bašić-Kinda.

  Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan-Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40-91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes.

Keywords:  ixazomib; lenalidomide; multiple myeloma; relapsed/refractory; retrospective study

DOI:  https://doi.org/10.3390/medicina60111905
Hematology. 2024 Dec;29(1): 2433172

Combining azole antifungals with venetoclax plus azacitidine in patients with newly diagnosed acute myeloid leukemia.

Xushu Zhong, Jia Wang, Yang Dai, Xiaoou Huang, Jiazhuo Liu, Bing Xiang, Hongbing Ma.

  The combination of venetoclax (VEN) with hypomethylating agents (HMAs) improves survival in patients with acute myeloid leukemia (AML) and may cause neutropenia requiring combined antifungal therapy or prophylaxis. The inhibition of cytochrome P450 activity by azole antifungal agents leads to elevated blood concentrations of VEN. This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine (AZA) with azoles in newly diagnosed AML patients. The primary endpoints included complete remission (CR), complete remission with incomplete blood cell recovery (CRi), composite CR (CRc, CR + CRi), blood cell recovery time and incidence of infections. The CRc was 50.0% in the azole group and 56% in the nonazole group (p > 0.05). In the azole group, the median recovery times for patients with ANC >500 cells/mm3 and ANC >1,000 cells/mm3 were 19 and 25 days, respectively. For the nonazole group, the corresponding times were 16 and 19 days (p < 0.05). In the azole group, the median durations for patients with a PLT >50,000/mm3 and >100,000/mm3 were 18 and 20 days, respectively. For the nonazole group, the corresponding times were 16 and 19 days (p > 0.05). The incidences of fungal and bacterial infections were not significantly different (30.8% vs 26.1% and 50.0% vs 56.0%) (p > 0.05). The cost-effectiveness ratio of the azole group is lower. There was no significant difference between VEN + AZA with or without azole in terms of efficacy, infection, or partial hematological toxicity. However, the combination of azoles may prolong the neutrophil recovery time. Azole combination could reduce the amount of venetoclax and improve health economics.

Keywords:  Acute myeloid leukemia; azacitidine; azole; efficacy; safety; venetoclax

DOI:  https://doi.org/10.1080/16078454.2024.2433172
Clin Lymphoma Myeloma Leuk. 2024 Nov 06. pii: S2152-2650(24)02401-7. [Epub ahead of print]

Characteristics and Treatment Patterns of Long-surviving Patients With Multiple Myeloma: Over 13 Years of Follow-up in the ConnectⓇ MM Registry.

Howard R Terebelo, James Omel, Lynne I Wagner, James W Hardin, Robert M Rifkin, Sikander Ailawadhi, Brian G M Durie, Mohit Narang, Kathleen Toomey, Cristina J Gasparetto, Prashant Joshi, Edward Yu, E Dawn Flick, Ying-Ming Jou, Hans C Lee, Rafat Abonour, Sundar Jagannath.

   BACKGROUND: Over the last 15 years, improvements in patient management and treatments have been associated with longer survival in patients with multiple myeloma (MM). The Connect MM Registry is a long-running, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM (NDMM). We assessed the demographics, clinical characteristics, and treatment patterns of long-term survivors (LTS) enrolled in this registry.
METHODS: Adults with NDMM (n = 3,011) were enrolled from 250 community, academic, and government sites across the US from 2009-2016. Baseline characteristics, treatment patterns, quality of life (QoL), and overall survival (OS) were examined among LTS, defined as patients with follow-up of ≥ 8 years after enrollment.
RESULTS: As of February 7, 2023, 518 patients were LTS and 2,493 were non-LTS. LTS were generally younger and had better performance status at enrollment compared with non-LTS. Most (65%) LTS received stem cell transplants and few (2%) experienced disease progression within 6 months of starting first line of therapy. At data cutoff, 63% of LTS were still on treatment at their most recent visit. QoL scores and QoL questionnaire completion rates were consistently higher among LTS than non-LTS. The estimated 8-year OS rate of all patients enrolled in the registry was 40%, comparable to an observed 8-year survival of 39% from the Surveillance, Epidemiology, and End Results (SEER) database.
CONCLUSION: This analysis provides insights on long-surviving patients with MM using real-world data and therefore presents generalizability beyond data obtained in long-term follow-up of clinical trials, underscoring the need for longitudinal follow-up through registries.

Keywords:  Newly diagnosed multiple myeloma; Registry; Stem cell transplant; Survival; Triplet therapy

DOI:  https://doi.org/10.1016/j.clml.2024.11.001