- |||||||||| Phase II Trial of Allogeneic Hematopoietic Cell Transplantation for Mature NK/T Cell Neoplasms (HCC Ballroom C; In-Person) - Dec 19, 2024 - Abstract #TCTASTCTCIBMTR2025TCT_ASTCT_CIBMTR_779;
P2
Conclusions Despite most patients being transplanted with high-risk, active disease, and significant comorbidities, outcomes were promising, providing compelling justification for the role of alloHCT in PTCL, even when remission is not obtained pre-HCT. The prospective study of alloHCT for PTCL is ongoing at NCI, aiming to decrease early TRM in older patients and further harness the graft-versus-tumor effect to afford cure and good survivorship.
- |||||||||| pentostatin / Generic mfg.
Pentostatin Low-Dose TBI Is an Effective Conditioning Regimen That Permits Donor Engraftment in Patients with High Co-Morbidities Undergoing the First Transplant or Prior to a Second Transplant () - Dec 7, 2024 - Abstract #ASH2024ASH_9351;
GvHD prophylaxis was reduced-dose post-transplant cyclophosphamide on days +3 and +4 (25 mg/m2, rPTCy) with 6 months of therapeutic levels of either sirolimus or tacrolimus and twice daily mycophenolate to day 35...Clinical outcomes were compared to similar patients receiving a Fludarabine and Melphalan (140 mg/m2) reduced intensity conditioning regimen who received full-dose PTCy (50 mg/m2 x 2 doses)...Pento/TBI conditioning with rPTCy is a promising approach appropriate for patients with significant co-morbidities undergoing first allogeneic transplant or patients who require a second or third transplant following primary graft failure/rejection or relapse. The kinetics of immune reconstitution based on serial blood mononuclear cells collected post-transplant will be presented.
- |||||||||| pentostatin / Generic mfg.
Journal: Biochemical Characterization of an Arabinoside Monophosphate Specific 5'-Nucleotidase-like Enzyme from Streptomyces antibioticus. (Pubmed Central) - Nov 27, 2024
To investigate the function of the gene penF in the pentostatin and vidarabine (Ara-A) biosynthetic gene cluster in Streptomyces antibioticus NRRL 3238, PenF was recombinantly expressed and characterized...Comparative sequence alignment and structural studies suggested that residues outside the primary substrate-binding site are responsible for this substrate specificity. In conclusion, PenF's activity toward vidarabine 5'-monophosphate likely plays a role in the dephosphorylation of precursors during Ara-A biosynthesis.
- |||||||||| Mavenclad (cladribine) / EMD Serono
Incidence of Second Primary Malignancies in Hairy Cell Leukemia: US Population-Based Study from 2000- 2021 (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6101;
It stresses the need for tailored surveillance protocols and preventive measures in the light of heightened susceptibility to specific malignancies in the critical years following their initial diagnosis. Furthermore, our results advocate for ongoing research into the mechanisms behind SPM development in this population and emphasize the integration of comprehensive long-term survivorship care into the broader framework of oncological treatment strategies.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Campath (alemtuzumab) / Sanofi, Jakafi (ruxolitinib) / Incyte
Survival and Therapeutic Outcomes in T-Cell Prolymphocytic Leukemia (T-PLL): A Collaborative Multi-Center Study Cohort (Pacific Ballroom Salons 15-17 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_2460;
Other active second-line treatments included : pentostatin (n=23; 44% ORR, 17% CR), ruxolitinib-based regimens (n=4; 25% ORR, 0% CR), venetoclax-based regimens (n=13; 39% ORR, 8% CR), bendamustine (n=10; 30% ORR, 0% CR), and nelarabine (n=4; 75% ORR, 50% CR)...Conclusions : In this large, multi-center study of T-PLL, frontline treatment with a combination of alemtuzumab/pentostatin improved response rates and OS...Intriguingly, TCL1A+, and CD4- T- PLL had worse OS/PFS, and scRNAseq confirmed unique molecular signatures in these populations, suggesting these represent novel molecular subtypes of T-PLL with prognostic significance. These studies form the foundation for future, targeted, therapeutic studies in this rare, aggressive disease with few treatment options.
- |||||||||| Rituxan (rituximab) / Roche
A Randomized Phase 2 Trial of 2nd-Line Cladribine with Concurrent or Delayed Rituximab in Patients with Classic Hairy Cell Leukemia (Marriott Grand Ballroom 11-13 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_2020;
Background : Hairy cell leukemia is a B-cell malignancy characterized by pancytopenia, splenomegaly, and long-term remissions to purine analogs cladribine (CDA) and pentostatin, but late relapses occur, presumably from minimal residual disease (MRD)...Two after CDAR vs 4 after CDA (p=0.42) progressed and required alternative therapy, several of whom remain MRD-free after moxetumomab pasudotox with rituximab...Thus, CDA with delayed rituximab at >6 months if/when blood becomes MRD-positive is still reasonable 2nd line treatment of HCL. Delayed rituximab is now being tested to eliminate MRD in patients who achieve MRD-positive CR to MEK +/- BRAF inhibition.
- |||||||||| pentostatin / Generic mfg., cordycepin (OVI-123) / OncoVista
Review, Journal: Insights into the methods for separation and chromatographic determination of nucleotides/nucleosides in Cordyceps spp. (Pubmed Central) - Sep 11, 2024
COR derived from adenosine and its structure is very similar to that of 2'-deoxyadenosine (2'-dA) and adenosine, resulting in an incorrect identification, which will influence its therapeutic effects. Therefore, this review primarily focused on the characteristics of Nt/Ns, the advanced methods, strategies, nanomaterials for extracting and determining Nt/Ns (COR in particular) in Cordyceps spp, as well as the methods for distinguishing COR from its structure analogs.
- |||||||||| Journal, Adverse events, Real-world evidence, Real-world: Assessing the risk of tumor lysis syndrome associated with the use of antineoplastic agents: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database. (Pubmed Central) - Sep 9, 2024
Further classifying the 164 antineoplastic agents into 46 chemical subgroups to conduct ADR signal detection, nitrogen mustard analogs were the most reported antineoplastic agent subclasses, followed by clusters of differentiation 20 inhibitors, and pyrimidine analogs, while clusters of differentiation 22 inhibitors were the antineoplastic agent subclass with the highest ADR signal strength, followed by podophyllotoxin derivatives and actinomycines. Our study showed the TLS risk characteristics of 164 antineoplastic agents by detecting and integrating ADR signals, which may help to optimize clinical practice.
- |||||||||| cyclophosphamide / Generic mfg., pentostatin / Generic mfg.
Trial completion date, Trial primary completion date: A Reduced-Intensity Conditioning Regimen (Cyclophosphamide, Pentostatin, Anti-thymocyte Globulin) Followed by Haploidentical Hematopoietic Stem Cell Transplant for the Treatment of Patients With Refractory or Recurrent Severe Aplastic Anemia (clinicaltrials.gov) - Aug 27, 2024
P1, N=6, Recruiting,
Although relapses are not uncommon, they can be effectively managed with cladribine, rituximab, or pentostatin. Trial completion date: Oct 2026 --> Jun 2027 | Trial primary completion date: Oct 2026 --> Jun 2027
- |||||||||| cordycepin (OVI-123) / OncoVista
Review, Journal: Cordyceps militaris: A novel mushroom platform for metabolic engineering. (Pubmed Central) - Jul 15, 2024
This review aims to describe specific and promising opportunities for the in-depth study and development of C. militaris as a new chassis cell. Additionally, to increase the practicability of this review, examples of the construction of cell factories are provided, and promising strategies for synthetic biology development are illustrated.
- |||||||||| cyclophosphamide / Generic mfg., pentostatin / Generic mfg.
Molecular Mechanisms of Anti-Host and Anti-Donor T Cell Tolerance in the MHC-Mismatched Mixed Chimeras Established with COH-MC-17 Regimen (Poster Hall, Exhibit Hall A, Level 2) - May 6, 2024 - Abstract #ATC2024ATC_464;
*Purpose: COH-MC-17 regimen consists of conditioning with low-dose cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) and infusion of CD4+ T-depleted hematopoietic graft. In the MHC-mismatched mixed chimeras established with COH-MC-17 regimen, absence of donor CD4+ T cells allows anti-host donor CD8+ T cells in the transplant to facilitate engraftment early after HCT and then become tolerant without causing GVHD; on the other hand, anti-donor host-type CD4+ and CD8+ T cells in the periphery are driven into FoxP3+ Treg cells in donor APC-dependent manner.
- |||||||||| ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION IN PATIENTS WITH ADVANCED MYCOSIS FUNGOIDES AND S (Hall 5) - Feb 14, 2024 - Abstract #EBMT2024EBMT_903;
Transplant from mMRD appears feasible, with 5-yr survival outcomes in between those form MRD and MUD and superimposable 5-yr CIR in patients with MRD and mMRD. Disease relapse remains the major cause of transplant failure, especially in patients with MF undergoing transplantation with active disease, making the post-transplantation disease treatment particularly challenging.
- |||||||||| cyclophosphamide / Generic mfg., pentostatin / Generic mfg.
Trial completion date, Trial initiation date, Trial primary completion date: A Reduced-Intensity Conditioning Regimen (Cyclophosphamide, Pentostatin, Anti-thymocyte Globulin) Followed by Haploidentical Hematopoietic Stem Cell Transplant for the Treatment of Patients With Refractory or Recurrent Severe Aplastic Anemia (clinicaltrials.gov) - Nov 18, 2023
P1, N=6, Not yet recruiting,
Our results suggest that pre-HCT fertility preservation should be offered regardless of regimen intensity, but also that there is potential for recovery in some patients years after HCT. Trial completion date: Sep 2025 --> Oct 2026 | Initiation date: Jun 2023 --> Jan 2024 | Trial primary completion date: Sep 2025 --> Oct 2026
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche, Zelboraf (vemurafenib) / Roche
Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia As a Marker of Tumor Burden with Prognostic Value and As a Tool for Disease Monitoring (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5854;
Among treated patients, 47/54 (87%) received cladribine and 7/54 (13%) pentostatin...A similar decrease in sIL-2R levels after therapy was observed in 4 relapsed patients treated with rituximab-vemurafenib (median pre-therapy sIL-2R 11.460 vs. 467 kU/L after treatment, p = 0.03; median reduction 10.848 kU/L)...While more data is required to validate its use in clinical routine, sIL-2R could be used as an effective marker for disease monitoring. Moreover, given the prognostic significance of post-therapy levels, sIL-2R may represent a prognostic factor alongside MRD to identify those patients that are more likely to develop early relapse.
- |||||||||| Campath (alemtuzumab) / Sanofi, Neupogen (filgrastim) / Kyowa Kirin, Amgen
Enrollment closed, Enrollment change, Trial primary completion date: Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease (clinicaltrials.gov) - Oct 27, 2023
P1/2, N=55, Active, not recruiting,
Relapsed patients had a poor outcome despite salvage therapy with only a 30% OS at 3 years. Recruiting --> Active, not recruiting | N=98 --> 55 | Trial primary completion date: Sep 2025 --> Jul 2023
- |||||||||| arecoline / Cogent Pharma
Preclinical, Journal: Arecoline aggravates acute ulcerative colitis in mice by affecting intestinal microbiota and serum metabolites. (Pubmed Central) - Jul 30, 2023
In summary, it was found that arecoline treatment exacerbated colonic injury and intestinal inflammatory responses in UC mice, disrupted the host's intestinal flora, and affected changes in flora metabolites, thereby exacerbating the development of colonic inflammation. Therefore, the consumption of betel nut can be associated with the risk of aggravating UC.
- |||||||||| How We Developed a Curative Therapy for CLL and Stopped Using It (Level 3, Hall B3) - Jun 21, 2023 - Abstract #SOHO2023SOHO_172;
Recent radical changes in the therapeutic landscape for CLL have led to current global treatment guidelines recommending the use of various highly effective targeted agents as frontline therapy,1,2 displacing previous chemoimmunotherapy (CIT) regimens such as fludarabine/ cyclophosphamide/rituximab (FCR)...In the late 1980's, three functionally similar agents related to purine nucleoside analogues entered clinical development; deoxycoformycin (DCF), 2-chlorodeoxy-adenosine (cladribine; 2-CdA) and 2-F-ara-adenosinemonophosphate (fludarabine; F). The first major report of F in relapsed/refractory CLL by Keating was truly remarkable in describing a 13% CR rate (overall response rate 57%).3 Cheson summarized this period as a "therapeutic beauty contest" among the three agents, that F ultimately emerged from victorious and became the foundational agent for subsequent combination development.4 As a single agent in frontline CLL, F improved PFS compared to chlorambucil (20 vs 14 months) and attained a CR rate of 20%.5 Elegant work in Plunkett's lab at MD Anderson established the synergy between F and DNA-damaging agents such as cyclophosphamide via inhibition of DNA repair,6 and at least 3 frontline trials have shown the superiority of the FC combination over single agent F, with CR rates as high as 39%, but modest overall survival impact.7 The new century brought the first therapeutic monoclonal antibody in cancer (rituximab; antiCD20) to be bravely applied in CLL by Byrd and O'Brien showing modest single agent activity, developing a safe infusion schedule to mitigate reactions, and establishing a dose response curve above the standard 375 mg/m2 lymphoma dose.8 Further laboratory studies showed bi-directional synergistic cytotoxicity with FC and R, both directly and through reduction in levels of surface complement defense proteins by F, and reduction in anti-apoptotic BCL2 protein levels by R.9 The resultant FCR regimen was pioneered at MD Anderson10 and subsequently shown in randomized trials in both frontline and relapse settings to deliver improved overall survival compared to FC and attain CR rates of up to 72% and the unprecedented attainment of uMRD (<10
- |||||||||| Lumoxiti (moxetumomab pasudotox) / AstraZeneca, Innate, Tafinlar (dabrafenib) / Novartis, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal, IO biomarker: Hairy Cell Leukemia: Where Are We in 2023? (Pubmed Central) - Apr 25, 2023
Purine nucleoside analogs remain the cornerstone of treatment, and the addition of rituximab has deepened and prolonged responses in the upfront and relapsed setting...Future efforts will focus on identifying patients with high-risk disease who require intensified regimens. Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Enrollment closed: A Blood Stem Cell Transplant for Sickle Cell Disease (clinicaltrials.gov) - Mar 3, 2023
P1, N=3, Active, not recruiting,
Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease. Recruiting --> Active, not recruiting
- |||||||||| Jakafi (ruxolitinib) / Novartis, Incyte
COMPARISON OF EFFICACY AND TOLERABILITY OF A RUXOLITINIB-BASED THERAPY VERSUS OTHER TREATMENT OPTIONS FOR STEROID REFRACTORY ACUTE GVHD IN A REAL LIFE EXPERIENCE (ePoster Area) - Feb 11, 2023 - Abstract #EBMT2023EBMT_1402;
Forty-nine out of 159 patients (31%) started a second-line (2L) therapy because of steroid refractoriness and 12 (24%) had a subsequent third-line (3L) therapy.Median age was 57 years (range 22-73), the underlying diseases were mainly acute leukemias (47%), 55% received a myeloablative conditioning regimen and 94% peripheral blood stem cells; overall, stem cells came from mismatched unrelated donors (47%), matched unrelated or sibling donors (39%) and haploidentical donors (14%).The 2L and 3L therapies used were: ruxolitinib monotherapy (13 patients), ruxolitinib in association with extracorporeal photopheresis (ECP) (11 patients), ECP (10 patients), ECP in combination with etanercept (6 patients) , etanercept monotherapy (17 patients), pentostatin (4 patients) (see table below)...Among CMV positive patients undergoing letermovir prophylaxis, a late CR-CMV occurring after day 100 was detected in 7 out of 10 patients (70%) during ruxolitinib-based treatment and in 2 out of 11 (18%) during other therapies (p=0.016).At a median follow-up of 19 months (range 4-84) after the start of 2L treatment, cumulative incidence of mortality at day 100 was 28% after ruxolitinib-based treatment and 31% after other therapies (p=0.551).One-year overall survival was 43%, without significant difference between ruxolitinib-based treatment and other therapies.GroupTreatmenttypeN. In our experience, a ruxolitinib-based therapy for SR-aGVHD resulted in a significantly higher OR rate at day 28 in comparison with other treatment options, while infectious complications and outcome didn
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