- Clinical and Epidemiological: Clinical, genetic and societal
- Therapies, Excluding Transplantation and Cellular Immunotherapies I
- Therapies, Excluding Transplantation and Cellular Immunotherapies II
Clinical and Epidemiological: Clinical, genetic and societal
Sumit Gupta, David T. Teachey, Meenakshi Devidas, et al.
The reasons for the outcome disparities between certain disadvantaged groups mentioned in the title of the study are different. According to the study authors, further studies are needed to identify specific causes for differences in survival so that the differences can be reduced through targeted interventions.
Biqi Zhou, Xinran Chu, Hong Tian, et al.
Age, extent of MRD, and DNA repair gene mutations are related to E2A-PBX1 positive B-ALL outcomes. Allo-HSCT, especially haploidentical-HSCT, would optimize the prognosis.
213 ASH denotes this abstract as clinically relevant:
Aman Wadhwa, Yanjun Chen, Lindsey Hageman, et al.
More research is needed to understand the mechanism of the relationship between morbid obesity during maintenance and the risk of relapse in children with ALL. The study shows that in the context of ALL maintenance therapy, morbid obesity is associated with relapses. There is also a lower systemic exposure to 6MP. Lower TGN (red cell thioguanine) values cannot explain the relationship between BMI and the risk of relapse.
Shaobo Li, Pagna Sok, Keren Xu, et al.
If, according to the DNA methylation data, increased B-cell proportions are found in newborns with Down syndrome (DS), this can be a risk factor for the development of DS-ALL in childhood. This finding should be investigated as a new biomarker for ALL risk in the non-DS population. However, it needs to be confirmed by conventional cell count measurements.
Corentin Orvain, Sylvain Chantepie, Xavier Thomas, et al.
Pediatric-inspired protocols in the treatment of young adults with ALL have a poor risk of CNS involvement and historical use of allogeneic SCT does not improve outcomes. Treatment regimens tailored to adults with CNS involvement need to be developed.
Sabina Chiaretti, Massimiliano Bonifacio, Roberta Agrippino, et al.
The incidence of SARS-CoV-2 infection in adult ALL patients does not differ significantly from that of the general population. The contagion - mostly during the second wave of the pandemic - was mainly nosocomial. The mortality was 11%. It follows that ALL should be treated mainly on an outpatient basis.
As observed earlier, it is striking that Ph + ALL patients were better cared for with fewer treatment interruptions. This points to an advantage of the TKI-based induction / consolidation strategy without systemic chemotherapy in Ph + ALL, which is used in the GIMEMA protocols (Gruppo Italiano Malattie EMatologiche dell'Adulto), and also establishes a possible protective function of TKIs in COVID-19-Infected patients.
614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies I
Inge M. Van Der Sluis, Paola De Lorenzo, Rishi Sury Kotecha, et al.
Blinatumomab plus Interfant06 backbone was very well tolerated. The authors speak of promising efficacy in terms of a high rate of complete MRD response and short-term event free survival. In historical controls, relapses are frequent and early in therapy. However, the low relapse rate after blinatumomab is remarkable, even if a longer follow-up period is yet missing. Based on the study results, blinatumomab will be introduced in the next Interfant21 protocol for all infants with newly diagnosed KMT2A-r-ALL.
362 ASH denotes this abstract as clinically relevant
Nicola Goekbuget, Matthias Stelljes, Andreas Viardot,et al.
This ongoing study presents promising preliminary results, including for those aged 45-55. This means that even adults beyond the variable AYA definitions can benefit from a pediatric protocol with an intensive and individualized ASP therapy. High rates of HemCR were found in almost all subgroups. The MolCR rates ranged from 41-74% and a significant proportion of the patients remained MRD low positive. The authors, therefore, emphasize the need for a detailed MRD classification.
A high proportion of patients were treated with MRD-based targeted therapy. For MolFail, the response to blinatumomab was lower compared to previous studies, and for MolFail T-ALL patients, the response to nelarabine was only 18%. On the other hand, the OS of MolFail patients with the combination of targeted therapy and SCT was promising. For the study authors, the SCT is therefore still a key component: It contributes to improved results, although the overall proportion of SCT was lower than in previous GMALL studies.
Patrick A. Brown, Lingyun Ji, Xinxin Xu, et al.
The blinatumomab arm was superior to the standard chemotherapy arm for patients with BM ± EM relapse. Thus, according to the study authors, blinatumomab is the new standard therapy for these patients. The blinatumomab arm, on the other hand, was not superior in IEM relapse. Better treatments are urgently needed for the subgroup of CNS relapse patients because a strikingly high rate of relapse has been observed in both arms.
Sujith Samarasinghe, Ajay Vora, Nicholas John Goulden, et al.
It is safe for low-risk patients to de-escalate therapy. High-risk patients, especially those with high-risk cytogenetics, can benefit from intensified therapy. This is the long term result of UKALL 2003.
Eleni Argyriadi, Ingo G. Steffen, Guenter Henze, et al.
Treatment delays did not affect the outcome. However, deviations from the protocol - a relevant part would be avoidable - did not significantly influence the remission rates, but they were significantly associated with inferior DFS. Strict adherence to the protocol should lead to improved results. Deviations from the protocol have a prognostic influence, especially in patients with late relapse with generally more chemosensitive diseases and a better prognosis.
Clare J Rowntree, Amy A Kirkwood, Laura Clifton-Hadley, et al.
ABP is an independent negative prognostic factor. Patients with T ALL and ABP were more than twice as likely to relapse. This is an indication to classify them as high-risk patients in future studies. Nelarabine according to ABP status does not appear to be of any benefit.
614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies II
Patrice Chevallier, Thibault Leguay, Michael Doubek, et al.
A very active and well-tolerated first-line therapy for older patients with CD22 + Ph-neg BCP-ALL is fractionated inotuzumab ozogamicin in reduced doses plus low-intensity chemotherapy.
Philippe Rousselot, Yves Chalandon, Sylvie Chevret, et al.
The combined administration of four cycles nilotinib plus chemotherapy have been shown to be very effective in bridging younger adults with Ph-positive ALL to SCT. If HD-AraC is omitted, the recurrence rate is higher despite the BCR-ABL1-MRD4 values that are non-inferior.
Nora Zieger, Maryam Kazerani Pasikhani, Tobias Straub, et al.
The study data suggest that TFI rejuvenates T cells (functionally and transcriptionally). After restimulation (day 21 TFI), T cells activate an effector program again. They are less exhausted compared to CONT-T cells. Further studies should identify gene clusters that are crucial for persistent T cell function. They might serve as targets that improve the efficacy of T-cell-based immunotherapies.
Kangyu Huang, Bingqing Tang, Zihong Cai, et al.
The study shows: The novel HDAC-selective inhibitor tucidinostat could specifically target the IKZF1del high-risk B-ALL by restoring IKZF1 expression. This would lead to a attenuation of the proliferation and a reversal of the Warburg effect and to an improvement in survival in the PDX model. A promising therapeutic strategy for B-ALL patients with changes in ICZF1 haploinsufficiency is emerging here.
Claire E. Pillsbury, Jairo A. Fonseca, Jodi Dougan, et al.
Siglec-15 is a novel, potent immunosuppressive molecule. It is active in the progression of leukemia and may be targeted to activate T lymphocytes against leukemia cells.
Andre Baruchel, Jonas Abrahamsson, Yves Bertrand, et al.
With a poor prognostic relapse rate, 7 out of 17 patients achieved CR + Cri (41.2%). The safety profile and exposure are consistent with the available adult data. Enrollment starts for patients under 2 years of age with R / R ALL or AML.