- |||||||||| Clinical, Review, Journal: How we treat patients with metastatic HER2-positive breast cancer. (Pubmed Central) - Mar 25, 2022
The randomized DESTINY-BREAST03 study compared trastuzumab deruxtecan (T-DXd) with trastuzumab emtansine (T-DM1) in patients previously treated with trastuzumab and a taxane...For subsequent lines, trastuzumab duocarmazine, neratinib plus capecitabine or the continuation of trastuzumab with different chemotherapy partners are valid options...For those relapsing between 6 and 12 months after non-pertuzumab-based adjuvant treatment, we recommend first-line THP. Finally, for patients with active brain metastasis, tucatinib-based combination represents a suitable second-line option.
- |||||||||| Melblez Kit (melphalan hepatic delivery system) / Delcath
Trial completion date, Trial primary completion date: FOCUS: Percutaneous Hepatic Perfusion in Patients With Hepatic-dominant Ocular Melanoma (clinicaltrials.gov) - Mar 24, 2022
P3, N=102, Active, not recruiting,
Finally, for patients with active brain metastasis, tucatinib-based combination represents a suitable second-line option. Trial completion date: Jul 2021 --> May 2023 | Trial primary completion date: May 2021 --> Jun 2022
- |||||||||| Review, Journal: Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. (Pubmed Central) - Mar 18, 2022
In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.
- |||||||||| Natesto (testosterone) / Acerus, Medac, Aytu BioPharma
Journal: Converting men from Clomiphene Citrate to Natesto for hypogonadism improves libido, maintains semen parameters, and reduces estradiol. (Pubmed Central) - Feb 3, 2022
Men on CC and Natesto reach eugonadal testosterone levels, however; on CC the E2 level nearly doubled from baseline, and converting men from CC to Natesto returned E2 to nearly baseline levels. There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility.
- |||||||||| Jivadco (trastuzumab duocarmazine) / Byondis, Medac
Enrollment closed, Combination therapy, Metastases: Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors (clinicaltrials.gov) - Feb 2, 2022
P1, N=120, Active, not recruiting,
There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility. Recruiting --> Active, not recruiting
- |||||||||| Natesto (testosterone) / Acerus, Medac, Aytu BioPharma
Journal: Men converting from clomiphene citrate to Natesto with a desire to maintain spermatogenesis should be followed closely. (Pubmed Central) - Feb 1, 2022
Testosterone deficient men interested in maintaining spermatogenesis who convert from CC to Natesto seeking a more robust symptomatic response should be followed closely with repeat serum gonadotropins and semen parameters to confirm that spermatogenesis is not being suppressed. Dose titration of Natesto may be effective at optimizing gonadotropins, semen parameter values, testosterone levels, and symptomatic response to treatment.
- |||||||||| Campath (alemtuzumab) / Sanofi
48 HLA-IDENTICAL RELATED HEMATOPOIETIC STEM CELL TRANSPLANTS IN SICKLE CELL DISEASE: IMPROVING RESULTS DURING THE LAST DECADE (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1773;
GvHD prophylaxis with cyclosporine and mycophenolate mofetil (MMF) (January 2015 – February 2019) or tacrolimus and MMF (February 2019 – December 2021). Seizure prophylaxis during immunosuppression: phenytoin until January 2015, afterwards levetiracetam... The outcome of our center, the larger HSCT series in Spain is similar to the international cohort and confirms the role of HSCT for children with SCD. Since 2015 we have improved our results, with less toxicity and without mortality.
- |||||||||| Campath (alemtuzumab) / Sanofi
WISKOTT ALDRICH SYNDROME CAUSED BY NOVEL WASP INTERACTING PROTEIN(WIP) MUTATION IS ASSOCIATED WITH JUVENILE MYELOMONOCYTIC LEUKEMIA - A CASE REPORT. (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1769;
The dysregulation in RAS signalling caused by mutations of NRAS, KRAS, PTPN11 and CBL and NF1 can be found in 90% of the cases of JMML.However, in the remaining 10% of patients without a molecular mutation, the diagnosis is largely reliant on a combination of clinical and laboratory observations, as stringently laid by the 2016 WHO criteria.It has been well recommended to consider Wiskott-Aldrich syndrome in male infants with JMML where none of the 5 canonical molecular mutations of JMML can be identified. Certainly, a strong degree of suspicion should be exercised and investigations for WAS-WIP complex mutations should be actively looked for, particularly in children in JMML where the classic driver mutation cannot be identified.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus
AN INTERNATIONAL MULTI-CENTRE REVIEW OF HAEMATOPOIETIC CELL TRANSPLANTATION FOR RIPK1 DEFICIENCY (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1765;
In cases where a related non carrier donor is not available, a heterozygous donor could be suitable as seen in our patient. Within the limitations of a retrospective small case series, the findings from this international, multi-centre review support the safety and efficacy of HSCT for RIPK1-deficiency, even with significant pre-transplant comorbidities.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus
CLINICAL AND IMMUNOLOGICAL OUTCOMES OF HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR INBORN ERRORS OF IMMUNITY: 20 YEARS’ EXPERIENCE FROM A MONOCENTRIC COHORT OF 220 PATIENTS (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1763;
On a 20-year experience on 220 IEIs patients, overall survival was 73,2%, with lower survival rate in patients treated with non-myeloablative regimens (p<0,001) or receiving HSCT without preconditioning regimen (p=0,047) rather than those treated with myeloablative conditioning with Busulfan (p<0,001) and Treosulfan (p=0,003) or Reduced Intensity Conditioning (RIC) (p=0,004).Graft failure occurred mostly in severe combined immune deficiency (SCID) patients, both T-B- and T-B+ (31,8% and 22,8% respectively), followed by combined immune deficiency (CID) patients (18,2%) and congenital defects of phagocyte and osteopetrosis (13,6%). Our results confirm the effectiveness of HSCT as a curative treatment for IEIs, with excellent long-term survival rate and effective immunological reconstitution.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus
THIOTEPA-TREOSULFAN-FLUDARABINE (TTF) AS CONDITIONING REGIMEN IN PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLOHSCT) FOR MYELOFIBROSIS OR MYELODYSPLASTIC SYNDROME: A SINGLE CENTER EXPERIENCE (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1696;
Therefore, the replacement of busulfan by treosulfan in a dual alkylator regimen with thiotepa and fludarabine (TTF) could be a promising toxicity-reduced but myeloablative conditioning regimen for a setting of patients characterized by an advanced median age and usually with high comorbidity index (HCTI), therefore at high risk for relapse and transplant-related mortality.To date no data about the use of a dual-alkylator treosulfan-based regimen are reported in this setting...Graft-versus-host disease (GVHD) prophylaxis consisted of a calcineurin inhibitor (8 pts cyclosporine, 1 pt tacrolimus) plus methotrexate and ATG for 9 patients, while combination of cyclosporine with micophenolate mofetil and post-transplant cyclophosphamide was used in a patient who underwent HSCT from a mismatched unrelated donor... These data suggest feasibility, safeness and efficacy of TTF myeloablative regimen for MF/MDS patients, with excellent early full donor engraftment and manageable transplant related toxicity. Larger cohort and longer FU are needed for survival analysis.
- |||||||||| Campath (alemtuzumab) / Sanofi
IMPROVEMENT IN ACUTE NEUROLOGICAL COMPLICATIONS RELATED TO STEM CELL TRANSPLANT IN SICKLE CELL DISEASE: LESSONS FROM OUR EXPERIENCE (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1695;
Also, GvHD prophylaxis used until 2019 was CsA and MTX, changing later to tacrolimus and mycophenolate mofetile (MMF).Seizure prophylaxis was provided during calcineurin inhibitors treatment, as well as maintenance of platelet threshold above 50.000/mcL, hemoglobin 11 g/dL and avoid hypomagnesemia.Epidemiological and clinical parameters were collected... Even with reduced-toxicity conditioning and the switch to tacrolimus, neurological events still happen. Recent modifications in our center, mainly since the implementation of ABPH, have decreased acute CSN complications and improved SCD event-free survival rates during transplant, with less toxicity, morbidity and mortality.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus
TREOSULFAN-BASED CONDITIONING FOR ALLOGENEIC HSCT IN CHILDREN: A CASE SERIES OF SINGLE CENTER EXPERIENCE (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1451;
The advantages of this regimen are low peri-transplant and early post-transplant mortality and the ability to induce 100% chimerism early after transplantation. We show that our experience HSCT using a treosulfan-based conditioning regimen is a safe treatment option in pediatric patients, even in those with high-risk clinical features pre-HSCT or those with no HLA-identical family donor.
- |||||||||| cyclophosphamide / Generic mfg., sirolimus / Generic mfg.
LOW DOSE ANTI T-LYMPHOCYTE GLOBULIN IN HIGH T-CELL CONTENT PBSC GRAFT: IMPROVING TRANSPLANT OUTCOMES IN POST-TRANSPLANT CYCLOPHOSPHAMIDE PLATFORM (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1436;
Long-term outcomes should be evaluated prospectively. Starting from 2019, 21 patients were transplanted using peripheral blood grafts containing more than 300*106/kg and were administered PT-Cy 50 mg/kg on day+3 and day+4 with the addition of ATLG 5 mg/kg on day+5 (Grafalon, Neovii) (study group)...In both groups, GvHD prophylaxis included sirolimus (with mycophenolic acid in HLA-mismatched and unrelated transplants)... Combining PT-Cy with low ATLG dose in high T-cell content PBSC graft translated into a low rate of chronic GvHD incidence, without impacting relapse incidence and survival outcomes.
- |||||||||| Campath (alemtuzumab) / Sanofi
COMPARISON OF FLUDARABINE/MELPHALAN(FLUMEL) WITH FLUDARABINE/MELPHALAN/BCNU OR THIOTEPA(FBM/FTM) IN PATIENTS WITH AML UNDERGOING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION – A REGISTRY STUDY ON BEHALF OF THE EBMT ALWP (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1426;
In previous studies, we compared two of the most used conditioning protocols from the intermediate TCI score based on one alkylating agent as fludarabine/melphalan (FluMel) vs. fludarabine/treosulfan (FluTreo) using the EBMT ALWP registry, which serve as basis for the comparison of the present study...Additional transplant characteristics as female donor (FBM/FTM: 28.2% vs. 32.4%, p=0.02), CR1 status at allo-HCT (FBM/FTM: 82% vs 78.1%, p=0.02), matched sibling donor (FBM/FTM: 21.1 vs. 31.7%, p<0.0001) and in vivo T-cell depletion (anti-thymocyte-globuline in 75.8% of FBM/FTM patients, alemtuzumab more used in 66% of FluMel patients) were different among cohorts... In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning seems to improve overall survival while maintaining similar toxicity in AML patients in CR undergoing allo-HCT. Due to several limitations of the study including the retrospective nature of the study and unbalanced patient characteristics, these data should be interpreted with caution.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus, Promacta (eltrombopag) / Novartis
HAPLOIDENTICAL STEM CELL TRANSPLANT IN PAEDIATRIC PATIENTS WITH RECURRENT OR TREATMENT-REFRACTORY SEVERE APLASTIC ANAEMIA AND REFRACTORY CYTOPENIA OF CHILDHOOD. (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1393;
Most of them were heavily pretreated patients, refractory to immunosuppressive treatment (8/9) and eltrombopag (7/9)...Conditioning was based on fludarabine+cyclophosphamide combination in all SAA patients and was myeloablative with busulfan/treosulfan + fludarabine+thiotepa in RRC patients... Haplo transplant offers a relatively successful therapeutic opportunity for refractory SAA/RIC, a subset of patients with limited curative alternatives. We observed excellent engrafting rates likely related to the addition of low dose radiotherapy to the conditioning.TRM was acceptable, and transplant-related microangiopathy was involved in the two cases. However, it is important to work forward to reducing transplant toxicity.We still face a significant rate of severe acute GVHD and, to a lesser degree, cGVHD that should be improved.The limited number of cases precludes us from assessing which Haplo platform is best suited for these patients. Longer follow-up is needed to assess QoL in patients treated with Haplo.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus, Grafalon (rabbit anti-T-lymphocyte globulin) / Mundipharma, NeoPharm
HAPLOIDENTICAL T CELL DEPLETED HSCT REPRESENTS A SAFE THERAPEUTIC ALTERNATIVE TO MSD TRANSPLANTATION IN PATIENTS WITH TRANSFUSION DEPENDENT THALASSEMIA (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1391;
Immunosuppression (IST) consisted in the majority of cases of tacrolimus (in two cases of cyclosporine A) and mycophenolate mofetil... These preliminary safety and efficacy data of T-haplo-HSCT are encouraging for a transplant indication without delay in TDT patients lacking a MD. Furthermore, treosulfan demonstrated to be an excellent alternative to busulfan, with no case of veno-occlusive disease in this high-risk patient population.
- |||||||||| sirolimus / Generic mfg.
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN WITH LYMPHOBLASTIC LYMPHOMA NOT ACHIEVING REMISSION (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1390;
Patient's characteristics >*HSCT1 – first transplantation, HSCT2-second transplantation, CNS-central nervous system, Status1-status prior to transplantation, Status2-status post transplantation, BM-bone marrow, MUD-matched unrelated donor, haplo-haploidentical, FluBu14 – fludarabine+busulfan 14 mg/kg, FluTreo36-fludarabine+treosulfan 36 mg/m2, FluMel-fludarabine+melphalan, NelMel-nelarabine+melphalan, PTCy-posttransplant cyclophosphamide, Tx-tacrolimus, sir-sirolimus, Mtx-metotrexate, CsA-cyclosporine A, S-stabilization, P-progression, CR-complete remission, PR-partial remissionAdministration of allo-HSCT resulted in remission induction in 4 children (3 CR and 1 PR). Allo-HSCT can induce durable remissions in children with progressive or stable disease R-R LL.
- |||||||||| Orencia (abatacept) / BMS, Actemra IV (tocilizumab) / Roche, JW Pharma
TCRΑΒ+/CD19+-DEPLETION IN SECOND ALLOGENIC HSCT IN CHILDREN ACUTE LEUKEMIA. (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1315;
17 pts received treosulfan-based preparative regimen, TBI regimen was used in 40 pts, 7 pts received others...Regimen 1 (n=13): thymoglobulin 5mg/kg, rituximab 200 mg/m2 and bortezomib on day +2, +5; regimen 2 (n=51): tocilizumab at 8 mg/kg on day -1 and post-transplant abatacept at 10 mg/kg on day +2, +7, +14, +28.TCR αβ+/CD19+ depletion of HSCT with CliniMACS technology was implemented in all cases... The present analysis of second allogeneic HSCT in children with AL supports the efficacy of this treatment option for a subset of patients.The depletion of TCR-alpha/beta and CD19 lymphocytes from the graft ensures high engraftment rate and acceptable TRM. TBI regimen may play a significant role in this cohort of patients.
- |||||||||| Campath (alemtuzumab) / Sanofi
RESIDUAL RECIPIENT T-CELLS ARE RESPONSIBLE FOR SEVERE LUPUS NEPHRITIS IN RALS-ASSOCIATED LUPUS NEPHRITIS PERSISTENCE AFTER ALLOGENEIC, MATCHED SIBLING DONOR TRANSPLANT. (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1302;
In view of refractory autoimmunity, he was treated with a matched sibling donor(MSD) bone marrow transplant with Fludarabine, treosulfan and thiotepa conditioning at 30 months of age...Consequently, he had recurrence of primary disease manifesting as monocytosis with splenomegaly alongside lupus nephritis.On account of refractory and severe, biopsy-proven lupus nephritis induced by the underlying RALD, he had a second MSD bone marrow transplant from a different sibling at 38 months of age with Fludarabine, busulfan and alemtuzumab conditioning...He has relapsed, persistent lupus nephritis and a recurrently raised titre of anti-DS-DNA antibodies, despite treatment with steroids, immunosuppresants, Rituximab, Bortezomib... HCT for treatment of autoimmunity in RALS has not been documented in literature to the best of our knowledge. Further data is needed to ascertain the unique complications associated with HSCT in RALS.While mixed T cell chimerism does not affect outcome in non malignant transplants in general, it is proposed that residual inflammatory activated autologous cells here drive persistent disease manifestations, and that full donor T cell chimersim is required to fully control disease.
- |||||||||| Ovastat (treosulfan) / Medac, Medexus, Grafalon (rabbit anti-T-lymphocyte globulin) / Mundipharma, NeoPharm
NEUROCOGNITIVE FUNCTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR SICKLE CELL DISEASE AND TRANSFUSION DEPENDENT THALASSEMIA (ePoster Area [VIRTUAL]) - Jan 30, 2022 - Abstract #EBMT2022EBMT_1100;
Within this pilot cohort of SCD and TDT patients, alloHSCT resulted in a stable common intelligence, while auditory short-term memory as well as fine motor skills improved. In contrast, cognitive processing speed and concentration worsened, which is in line with another publication from Scherwath et al (Psychooncology, 2013) reporting concentration issues after alloHSCT for hematologic malignancies, probably due to the toxicity of the transplant procedure independent of the underlying disease.
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