Myleran (busulfan) / Waylis Therapeutics - LARVOL DELTA

Discontinuation of Maintenance Therapy Guided by Minimal Residual Disease in Newly Diagnosed Multiple Myeloma: Long-Term Results of the GEM2014MAIN Study (IMS 2026) - " The GEM2014MAIN clinical trial randomly assigned lenalidomide and dexamethasone (RD) vs. ixazomib plus RD (IRD) as maintenance therapy in patients who received 6-cycles of induction therapy with bortezomib, lenalidomide and dexamethasone (VRD), followed by high-doses of melphalan or busulfan/melphalan and 2 consolidation cycles with VRD (GEM2012MENOS65 trial). Patients with MRDneg after two years of maintenance discontinued therapy and showed a significantly longer PFS than those with positive MRD that remained on maintenance. About half of the patients who were MRDneg at 2 years and discontinued maintenance remained alive and progression-free after 7 years and could be considered operationally cured."

Clinical • Minimal residual disease • Residual disease • Hematological Malignancies • Multiple Myeloma

Hematopoietic stem cell transplantation for acquired aplastic anemia in 2024: Report from the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG). (PubMed, Cancer Lett) - "Low-dose busulfan was frequently used in conditioning regimens for both platforms...Moreover, modern HCT practice supports broader consideration of transplantation for older patients, especially those aged 40-50 years. In conclusion, our report offers a comprehensive overview of the current HCT landscape in China and serves as a valuable resource for global practice."

Journal • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

Comparing the Predictive Performance of Machine Learning Models with a Newly Developed Population Pharmacokinetic Model for Busulfan in Paediatric Patients. (PubMed, Clin Pharmacokinet) - "A new popPK model was developed to support individualised dose adjustments in children using fewer blood samples. Both Random Forest and XGBoost could predict busulfan's plasma concentration with performance like that of the popPK model (population prediction). However, a larger dataset is needed for ML methods to describe a complete pharmacokinetic profile."

Journal • PK/PD data • Pediatrics • Transplantation

Long-Term Follow-Up of Busulfan Plus Cyclophosphamide and Etoposide Versus High-Dose Melphalan as Conditioning in Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma (IMS 2026) - " A total of 35 patients with multiple myeloma, enrolled between March 2016 and September 2021, patients aged 47-67 (median 57 years) with multiple myeloma were enrolled to receive bortezomib, thalidomide and dexamethasone (VTD) induction followed by ASCT. Our study showed that BuCyE is an effective and well-tolerated alternative to HDMEL conditioning, with good PFS."

Hematological Malignancies • Multiple Myeloma • Transplantation

Moderate Incidence but Striking Correlation with TBI of Secondary Malignancies after HSCT in Children with ALL: Long-Term Follow-up from the Prospective International BFM- and Forum-Trials (ASH 2023) - "Only pts with contraindications for TBI received chemo-conditioning, which consisted of i.v. busulfan, cyclophosphamide and etoposide. In the FORUM trial pts >4y of age were randomized to receive either TBI- or chemo-based conditioning regimens; pts 2 y of age at HSCT (94%, n=2024). TBI-based conditioning was applied in 64% (n=1429), while 34% (n=722) of pts received chemo-conditioning."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Basal Cell Carcinoma • Bone Marrow Transplantation • Brain Cancer • Breast Cancer • Chronic Graft versus Host Disease • CNS Tumor • Endocrine Cancer • Glioblastoma • Graft versus Host Disease • Hematological Malignancies • Leukemia • Non-melanoma Skin Cancer • Oncology • Pediatrics • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma • Transplantation • TP53

Comparison of Thiotepa, Busulfan, and Cyclophosphamide Versus Busulfan and Thiotepa Conditioning Regimens in Autologous Stem Cell Transplantation for Primary CNS Lymphoma: A Multicenter Retrospective Analysis. (PubMed, Hematol Oncol) - "We retrospectively analyzed patients aged ≤ 60 years who underwent ASCT with thiotepa-busulfan-cyclophosphamide (TBC) or busulfan-thiotepa (BuTT) conditioning after high-dose methotrexate-based induction at two Korean institutions between 2015 and 2023...In younger patients with PCNSL, TBC demonstrated a trend toward more durable disease control than BuTT, with manageable toxicity. As the thiotepa dose represents the major distinction between regimens, dose-intensified thiotepa strategies with adjusted partner agents merit further prospective investigation."

Clinical • Journal • Retrospective data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Transplantation

Ixazomib Plus Lenalidomide/Dexamethasone (IRd) Versus Lenalidomide /Dexamethasone (Rd) Maintenance after Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Results of the Spanish GEM2014MAIN Trial (ASH 2021) - "Background: The Spanish Myeloma Group (GEM) demonstrated that post-transplant maintenance with thalidomide plus bortezomib was superior to thalidomide alone, although this combination was associated with a high rate of peripheral neuropathy...Patients : Patients who where at least with stable disease after the GEM2012menos65 trial that included VRD-GEM induction, autologous hematopoietic stem cell transplantation conditioned with either melphalan-200 or intravenous busulfan together with melphalan-140 and consolidation with VRD-GEM were randomized to receive maintenance treatment with IRd versus Rd... After a median follow-up of 56 months, there was no difference in PFS between the two maintenance arms (median not reached, PFS at 5 years: 62% vs. 63% with IRd and Rd, respectively, p=0.785) (figure 1). In the overall series, there were no significant differences in PFS or OS among patients with standard (SR) or high-risk (HR) cytogenetics."

Clinical • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Pain • Plasmacytoma • Thrombocytopenia • Transplantation

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study. (PubMed, J Clin Oncol) - "Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT)...Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses."

Journal • P2 data • Bone Marrow Transplantation • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

NCI-2018-01752: Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Fred Hutchinson Cancer Center | Recruiting ➔ Active, not recruiting | N=68 ➔ 45

Enrollment change • Enrollment closed • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Burkitt Lymphoma • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Mast Cell Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • HLA-B • HLA-C • HLA-DRB1

Myeloablative Fractionated Busulfan Conditioning Regimen with Venetoclax in Patients with AML/MDS: Prospective Phase II Clinical Trial (TCT-ASTCT-CIBMTR 2022) - P2 | "Then, inpatient fludarabine 10 mg/m 2 , and cladribine 10 mg/m 2 were given followed by Bu on days -6 to -3. Venetoclax can be safely added to the fractionated busulfan regimen. Early data on efficacy appear promising."

Clinical • P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Immunology • Mucositis

Genetic Engineering of Hematopoietic Progenitor Stem Cells for Targeted IFN-α Immunotherapy Reprogramming the Solid Tumor Microenvironment: A First-in-Man Study in Glioblastoma Multiforme (NCT03866109) (ASH 2023) - P1/2 | "Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector. So far, up to 3 million Temferon cells/kg have been co-administered with a fixed dose of non-manipulated CD34+ supporter cells following a sub-myeloablative conditioning regimen (Thiotepa + BCNU or Busulfan or Busulfan alone)... These data show that Temferon is safe and biologically active at the tumor site and favors anti-tumor immunity. The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients and to counteract disease progression and improve the survival of uMGMT GBM patients."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • CNS Tumor • Gene Therapies • Glioblastoma • Oncology • Solid Tumor • CD34 • CD8 • IFNA1 • MGMT • PTPRC

Busulfan, melphalan and carfilzomib high-dose chemotherapy and autologous haematopoietic stem cell transplantation in multiple myeloma. (PubMed, Br J Haematol) - "We previously reported that the addition of bortezomib to BuMel improved PFS compared to melphalan alone in CIBMTR-matched controls. 80% of all patients and 82% of patients in the MTD cohort achieved MRD negativity. Further studies regarding this regimen are planned."

Journal • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Mucositis • Multiple Myeloma • Neutropenia • Oncology • Transplantation

High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial. (PubMed, Blood) - P3 | "We compared BUMEL vs. MEL200 outcomes in newly diagnosed multiple myeloma (NDMM) patients receiving intensified bortezomib, lenalidomide and dexamethasone (VRD) induction and consolidation therapy. After a median follow-up of 8.4 years, GEM2012 reported one of the longest PFS durations in NDMM patients, with BUMEL significantly favoring advanced ISS stages. The trial is registered at ClinicalTrials.gov (NCT01916252) and EudraCT (2012-005683-10)."

Journal • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Post–Allogeneic Stem Cell Transplant Clonal Plasma Cell Dyscrasia Presenting as Hepatic Dysfunction in a Patient With Triple-Negative Primary Myelofibrosis: Sinusoidal CD56+ Lambda-Restricted Plasmacytic Infiltration With Progressive Fibrosis Remodeling (SOHO 2026) - "Bortezomib therapy led to paraprotein reduction and regression of marrow fibrosis from MF-3 to MF-1...In late 2025, worsening liver function and biochemical progression prompted initiation of daratumumablenalidomide-dexamethasone...Recognition of this entity is important when evaluating unexplained hepatic dysfunction after transplantation. Flu/Bu/AGT: fludarabine/busulfan/antithymocyte globulin."

Clinical • Chronic Eosinophilic Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Plasmacytoma • NCAM1

Myeloablative fractionated busulfan, fludarabine, cladribine, thiotepa, and venetoclax (Cladillac) conditioning for high-risk AML: A phase 2 trial (ASH 2025) - P2/3 | "To reduce GVHD-associated morbidity and mortality, weincorporated post-transplant cyclophosphamide (PTCy)...GVHD prophylaxis consisted of PTCy 50mg/kg on days +3 and +4, tacrolimus ± mycophenolate mofetil... This study met its primary endpoint, demonstrating a promising 3-year PFS of 58% in acohort of patients with very high-risk AML. Outcomes were particularly favorable in TP53 wild-typepatients, with a low relapse rate of 13% and 3-year OS of 74%. These findings support furtherinvestigation of this novel conditioning regimen."

P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • FLT3 • TP53

Safety and Efficacy of a New High-Dose Chemotherapy Regimen of Panobinostat, Gemcitabine, Busulfan and Melphalan (Pano/GBM) with Autologous Stem Cell Transplant (ASCT) for Patients with High-Risk or Refractory/Relapsed Myeloma – Matched Pair Comparisons with a Concurrent Control Cohort. (TCT-ASTCT-CIBMTR 2023) - P2 | "The benefit in ASCT-1 of study patients was also seen over those controls who received BuMel in PFS (P<0.01) and OS (P<0.01). CONCLUSIONS : Pano/GemBuMel is safe and effective in HR or R/R MM, with better outcomes after ASCT-1 than matched concurrent controls."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Mucositis • Multiple Myeloma • Oncology • Transplantation • SLC1A5

TTBF-Aged SAA: Thiotepa-Based Conditioning for Haploidentical HSCT in Older Patients With Severe Aplastic Anemia (clinicaltrials.gov) - P=N/A | N=10 | Not yet recruiting | Sponsor: Peking University People's Hospital

New trial • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Transplantation

BUMEL vs MEL-200 prior autologous transplant for patients with newly diagnosed multiple myeloma previously treated with bortezomib, lenalidomide and dexamethasone: final results of a phase 3 trial (IMW 2022) - "Attempts to improve this conditioning have included TBI plus melphalan 140 mg/m2, and particularly the busulfan plus melphalan combination (BUMEL), among others... This is an open label, randomized phase 3 study followed by a maintenance trial that compared lenalidomidedexamethasone +/- ixazomib (Rosiñol L. et al...One patient in the BUMEL group had a graft failure successfully treated with cyclosporin... This randomized trial indicate that MEL200 should remain as the standard of care based on efficacy and toxicity, except for high-risk ISS patients, in which BUMEL provides a clear PFS benefit."

Clinical • P3 data • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Mucositis • Multiple Myeloma • Oncology • Transplantation • CD34

Diagnosis and treatment of familial hemophagocytic lymphohistiocytosis with isolated central nervous system involvement: A case report. (PubMed, Ann Hematol) - "The patient received a conditioning regimen comprising thiotepa, etoposide, busulfan, cyclophosphamide, and antithymocyte globulin (TT/VP16/BU/CY/ATG)...Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX)...At the last follow-up on day 679, the patient remained alive without neurological relapse or systemic HLH. In conclusion, this patient achieved long-term CNS remission and correction of the underlying molecular defect following allogeneic HSCT with a TT/VP16/BU/CY/ATG conditioning regimen."

Journal • Bone Marrow Transplantation • Graft versus Host Disease • Hemophagocytic lymphohistiocytosis • Immunology • Rare Diseases • Transplantation • CD34 • UNC13D

FORUM: Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P2/3 | N=1800 | Recruiting | Sponsor: St. Anna Kinderkrebsforschung | Trial primary completion date: Jun 2025 ➔ Jun 2030

Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701) (ASH 2025) - P2 | "Based upon retrospectivedata showing low rates of relapse, we hypothesized that patients with negative pre-HCT MRD by next-generation-sequencing of IgH B-cell receptor rearrangements (NGS-MRD) could achieve 2-year EFSexceeding 75% with a non-TBI regimen, an outcome comparable to those receiving TBI-based regimens. The Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) conducted a phase IIprospective trial at 45 Centers in North America (ONC1701 EndRAD: NCT03509961) between 2018 and2025 to evaluate outcomes of myeloablative non-TBI conditioning regimens for allogeneic HCT in B-ALLpatients at lower risk for relapse defined by absence of NGS-MRD (Clonoseq) of B-cell receptorrearrangements (BCR) just prior to HCT...Mismatched related/haploidentical grafts received post-transplant cyclophosphamide orTCRαβ/CD19 depletion according to institutional preference...Of patientsenrolled, 33% were White/Non-Hispanic, 37% Hispanic, 12% Black or African American, and..."

Biomarker • Clinical • IO biomarker • Minimal residual disease • Next-generation sequencing • Residual disease • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation

Phase II Trial of Venetoclax (Ven) in Combination with Azacitidine (AZA) As Maintenance Therapy for High-Risk Acute Leukemia Following Allogeneic Stem Cell Transplantation (SCT) (ASH 2022) - "The majority (63%) received a myeloablative intensity conditioning regimen using intravenous busulfan...After the protocol amendment for VEN to be given as 50 mg on days 1-7 on posaconazole, the requirement for dose changes decreased though still some patients required lower doses of VEN (as 30 mg on days 1-5) on subsequent cycles... Post-SCT maintenance therapy with VEN/AZA was safe and tolerable with favorable results in patients with high-risk AML and ALL. The majority of reported AEs was related to myelosuppression which is a known complication of VEN. Many patients required dose modification of VEN and treatment delays between cycles, highlighting the importance of monitoring these patients very closely."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Transplantation

Preliminary Safety and Efficacy of Myeloablative Orca-Q in Patients With Haploidentical Donors (SOHO 2026) - P1 | "All participants received MAC with one of the following: busulfan/fludarabine/thiotepa-based, TBI/fludarabine/thiotepa, or TBI/fludarabine. The study demonstrated high engraftment rates, encouraging OS and RFS, and low incidences of severe aGVHD and cGVHD. Outcomes appeared favorable in the TBI/fludarabine/thiotepa subgroup, with improved survival, GRFS, and lower relapse incidence, compared with other regimens. These findings support the safety and efficacy of Orca-Q in reducing GVHD and achieving durable remissions."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

OBSERVATIONAL COMPARISON OF OVERALL SURVIVAL BETWEEN PHASE 1B ORCA-T® AND REGISTRY-BASED POST-TRANSPLANT CYCLOPHOSPHAMIDE PATIENTS (EBMT 2025) - P1 | "Additionally, MAC regimens for the Ph1b' cohort were limited to busulfan/fludarabine/thiotepa, or total body irradiation (TBI)/cyclophosphamide, or TBI/etoposide between 2019-2024. Comparison of Orca-T phase 1b and PTCy patients from the CIBMTR registry demonstrated higher OS for Orca-T patients. The study was limited to OS and retrospective data, and further analysis is needed to explore factors like infection, relapse, and organ toxicity. A phase 3 randomized trial comparing Orca-T with single agent tacrolimus to conventional transplant with tacrolimus/methotrexate GvHD prophylaxis has recently completed accrual."

Clinical • P1 data • Post-transplantation • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Autologous stem cell transplantation with thiotepa, busulfan, and cyclophosphamide conditioning in patients with central nervous system lymphoma: a phase II study. (PubMed, Ann Hematol) - P2 | "The conventional busulfan dose (9-day regimen) may be associated with higher toxicity, suggesting the potential need for a modified TBC regimen in Asian populations. Further studies are needed to identify the optimal thiotepa-based conditioning in CNSL."

Journal • P2 data • Bone Marrow Transplantation • CNS Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Transplantation