TEST:

clonoSEQ

P=N/A, N=60, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P2, N=57, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Feb 2026 --> Aug 2026 | Trial primary completion date: Feb 2024 --> Aug 2024

To compare overall survival (OS) in frail or selected intermediate fit NDMM participants treated with VRd-Lite induction followed by lenalidomide maintenance (Arm 1) versus DRd induction followed by lenalidomide and daratumumab and hyaluronidase fihj maintenance (Arm 3). Among the three evaluable patients on the DRD-R arm, one has experienced a Grade 4 adverse event as maximum grade (hematologic). Among the two evaluable patients on the DRD-DR arm, one has experienced a Grade 4 adverse event as maximum grade (hematologic).

In conclusion, idiopathic hypertrophic pachymeningitis can present in children and should be considered in the differential for intradural masses.

Due to small sample size and lower than expected relapse, we were unable to demonstrate conversion of dMRD to uMRD using MN. However, this pilot study did confirm high correlation of uMRD and dMRD status with disease free survival and clinical relapse within 4 months, respectively. If strong negative predictive value is confirmed in a larger study, ctDNA MRD testing may be used to spare pts from imaging or to guide additional work up in pts with inconclusive findings on scans.

Based on the EPCORE-NHL-1 study, one of the first pivotal studies to report MRD in pts with R/R FL, epcoritamab drives rapid, deep, and sustained responses as supported by MRD assessment by both PBMC and ctDNA. MRD results correlate with clinical outcome, and achieving MRD negativity is associated with longer PFS. PFS was similar among all pts who achieved MRD negativity, including those with high-risk disease.

P2; Recruiting --> Active, not recruiting | N=24 --> 35

The evaluation of B-ALL MRD using MFC is a challenging endeavor, especially when the patient's LAIP changes after chemotherapy. Utilizing overlays with DFN and LAIP aids in the detection of MRD, as immunophenotypic patterns can be visualized and compared simultaneously.

P=N/A; Trial completion date: Mar 2024 --> Feb 2025 | Trial primary completion date: Mar 2024 --> Feb 2025

P2; N=50; Not yet recruiting; Sponsor:C. Babis Andreadis

We analyzed 234 cases of lymphoma (189 LBCL, 20 FL, 25 MCL) treated with commercial CAR19 (100% axi-cel and brexu-cel)...Additional profiling of the B- and T-cell tumors is ongoing and will be presented to discern a shared lineage implicating infidelity or trans-differentiation versus an unrelated secondary malignancy. These additional studies in progress include direct DLBCL vs TCL comprehensive genotyping, scDNA sequencing of marrow lymphocytes and progenitors, EBV genotyping and terminal repeat analysis, and retroviral insertion site mapping.

P1/2; Trial completion date: Apr 2023 --> Jun 2026 | Trial primary completion date: Apr 2023 --> Sep 2025

Our study demonstrates the potential of cfWGS as a sensitive method for MRD detection in MM. Specifically, cfWGS aligned with clinical MRD in 7/12 BM and 8/12 blood-derived mutation profiles. 8/9 divergences occurred in clinically negative samples, possibly due to inadequate BM affecting LOD.

Our data suggest that the clonoSEQ MRD assay is an effective surveillance tool for MCL patients following first-line therapy and is predictive of relapse prior to imaging.

P2; Not yet recruiting --> Recruiting

Our results show strong correlation between COG MFC and ClonoSEQ (r = 0.96), and both methods are complementary. Clonal evolution may occur, and blinatumomab immunotherapy may impact MFC B-ALL MRD evaluation.

P1; Not yet recruiting --> Recruiting

P2; Not yet recruiting --> Recruiting

In B cell ALL, Blinatumomab may offer a CIR benefit to pts with low levels of MRD detected on clonoSEQ.

"Adaptive Biotechnologies Corporation...announced new data demonstrating the expanding use of Adaptive’s next-generation sequencing (NGS)-based clonoSEQ® test in assessing minimal residual disease (MRD) in blood cancer patient care and in clinical trials. The data are being presented in more than 30 abstracts at the 65th Annual Meeting of the American Society of Hematology (ASH), December 9-12 in San Diego, California."

P2; Recruiting --> Active, not recruiting

P2; Trial completion date: Oct 2026 --> Jan 2027 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2026 --> Jan 2027

"Adaptive Biotechnologies Corporation (Nasdaq: ADPT), a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, together with its collaborators will present data from more than 30 abstracts demonstrating the actionability of Adaptive’s next-generation sequencing (NGS)-based clonoSEQ^® test in assessing minimal residual disease (MRD) in blood cancer patients at the 65th Annual Meeting of the American Society of Hematology (ASH), December 9-12 in San Diego, California."

P2; Trial completion date: Oct 2025 --> Feb 2026 | Trial primary completion date: Oct 2023 --> Feb 2024

Introduction: Fludarabine and cyclophosphamide (Flu/Cy) lymphodepletion (LD) prior to chimeric antigen T-cell (CAR T) infusion favorably impacts CAR T expansion and efficacy...Three deaths (2 Cla/Cy) occurred before day 100, all due to refractory fungemia post anakinra... Cla/Cy LD prior to brexu-cel is feasible in ALL and MCL patients with comparable efficacy. Toxicity rates including CRS, ICANS and early infections were similar to those seen with Flu/Cy, but there was a trend towards earlier recovery of neutrophils, B-, and T-cells with Cla/Cy. The trend was demonstrable even in patients at high risk of prolonged post-CAR T neutropenia as identified by the HS.

In B cell ALL, Blinatumomab may offer a CIR benefit to patients with low levels of MRD as detected on clonoSEQ.

No pts with uMRD by ctDNA had clinical relapse on study during 2 year follow up, confirming uMRD correlates with disease free survival. If a strong negative predictive value is confirmed in a larger study, ctDNA MRD testing may be used to spare pts from imaging or to guide additional work up in pts with inconclusive findings on scans.

We found a considerable degree of discordance between BCR-ABL PCR and NGS in Ph+ ALL patients. The most common discrepancy was PCR detectable / NGS undetectable, and in case of discordance, PCR positive results are most frequently given precedence in guiding clinical management. In the discordant patients, the presence of MRD positivity via either test drove changes to treatment rather than MRD negativity in one of the two tests.

One regimen that is commonly used is a combination of targeted therapies along with reduced intensity chemotherapy (inotuzumab ozogamicin, rituximab (if CD20+), blinatumomab and mini hyper fractionated cyclophosphamide, vincristine, and dexamethasone [Mini-HCVD]), which has demonstrated both improvements in survival while reducing treatment related toxicity. This retrospective single institute study demonstrates that the clinical outcomes of Mini-HCVD plus immunotherapeutic agents in older adults with Ph- ALL are similar to modified BFM backbone with reduced incidence of toxicity. While limited by small numbers, these results suggest that reduced intensity chemotherapy in combination with novel targeted agents could represent a new standard of care regimen in this historically difficult to treat patient population.

One of the patients with refractory disease underwent further therapy with blinatumomab, inotuzumab, CAR-T and allogeneic stem cell transplantation and is alive at 16 months from diagnosis...Noteworthy adverse effects include neutropenic fever (65%), liver function tests (LFT) abnormalities (70%), and neuropathy from vincristine (70%). Peg-asparaginase administration was associated with pancreatitis in 12%, thromboembolism in 30% and hypersensitivity reactions in 24% requiring switching to alternative forms of asparaginase products (erwinia and Rylaze)... The pediatric-inspired regimen CALGB 10403 was safe and efficacious in our AYA Ph- ALL population with no deaths due to treatment and a 5-year overall survival of 94%. Toxicities, especially from peg-asparaginase, should be closely monitored. While most patients will attain durable remission/cure, the minority with refractory or relapsed disease can still be successfully salvaged to achieve long term survival.

Introduction: DARA plus bortezomib, thalidomide, and dexamethasone (D-VTd) quadruplet therapy has shown clinical benefit versus VTd alone and is approved for transplant-eligible pts with NDMM. DARA SC combined with VRd in transplant-eligible pts with NDMM significantly improved PFS and increased depth of response (≥CR and MRD negativity), with consistent PFS benefit across clinically relevant subgroups. The safety profile was consistent with the known safety profiles for DARA SC and VRd. These data, together with results from the phase 2 GRIFFIN study, demonstrate the consistent and clinically meaningful benefit of quadruplet DARA plus VRd followed by D-R maintenance versus triplet VRd followed by R maintenance and support the combination of DARA plus VRd followed by D-R maintenance as a new standard of care for transplant-eligible NDMM.

Lenalidomide-dexamethasone (Rd) has represented a standard of care for transplant-ineligible (NTE) newly diagnosed multiple myeloma (NDMM) patients (pts) until the recent introduction of daratumumab (Dara) in the frontline setting. In the KRd vs Rd arms, 33/42 (78.6%) vs 19/40 (47.5%) pts are still under treatment; reasons for discontinuation were medical decision (1 vs 4), death (2 vs 4), adverse events (2 vs 1), progressive disease (3 vs 10), lost to follow-up (1 vs 0) and consent withdrawal (0 vs 2). The analysis of the primary MRD endpoint is planned when all pts have received treatment for 2 y (Q4 of 2023): results will be presented at the meeting.

"Adaptive Biotechnologies Corporation...today announced a multi-year, global translational collaboration with BeiGene to assess minimal residual disease (MRD) using clonoSEQ^® assay technology across the company’s pipeline of treatments for patients with lymphoid malignancies....This multi-year agreement will cover existing and future programs and adds to Adaptive’s growing list of translational collaborations with biopharmaceutical companies. As part of the collaboration, MRD status based on Adaptive’s clonoSEQ assay may be used as an endpoint in certain clinical trials to assess the depth and duration of response to BeiGene’s investigational medicines in patients with lymphoid malignancies. Adaptive will receive an upfront payment and will be eligible to receive future milestone payments upon achievement of specific regulatory milestones in certain geographies. Specific financial terms of the agreement will not be disclosed."

Overall, 1535 ID samples have been received and included several different sample tissues and preparation methods. 1285 (83.7%) of these calibrated. Calibration was most successful in FFPE and gDNA preparations from lymphatic tissue or extranodal masses with 806/883 (91.3%).

34 pts (81%) underwent SC collection, all with plerixafor (median yield 8.91x106 CD34+/kg). Extended frontline Dara-KRd for NDMM without ASCT induced high rates of sCR and/or MRD(-) within 8 cycles, meeting the primary endpoint. The rate and depth of MRD(-) improved beyond C8. This ASCT-free approach led to lower PFS for pts with 2+ HRCA, as also seen with ASCT, but excellent PFS in those with standard-risk disease and 1 HRCA.

Bendamustine/rituximab (BR) is a standard non-intensive regimen for MCL, and use of MT remains controversial...The GALLIUM study (Marcus R, et al, N Engl J Med 2017) previously showed improved PFS with a bendamustine/obinutuzumab (BO) induction compared with BR in follicular lymphoma, and we postulated this benefit may be observed in MCL... Omission of MO in pts achieving MRD- status after induction/CO did not result in worsening PFS. Observed PFS and toxicities with BO induction and CO appears comparable with other data sets utilizing a BR-based induction +/- MT in older, less fit MCL pts. Correlation between PFS and PB MRD testing after C2 induction therapy represents a potential new prognostic marker of MCL behavior, and may be an important early disease indicator in development of risk-adapted therapies.

SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with CHOP-RIT (CHOP + I133-tositumomab) in patients with FL. Despite a relatively high failure rate to detect trackable sequences using current technology (~29%), MRD assessment by NGS is a promising prognostic tool in FL. *co-senior authors

Fludarabine/cyclophosphamide lymphodepletion was started during MF to facilitate fresh infusion in eligible pts...Both received only a single dose of intrathecal hydrocortisone (no systemic steroids) with resolution of neurotoxicity within 24 hours of administration... Bispecific LV20.19 CAR T-cells with adaptive MF process is feasible, safe, and efficacious for R/R MCL with ORR 100%, no Grade 3+ CRS and low rates of Grade 3+ ICANS (12%). Adaptive MF enriched the final product with higher percentages of T-SCM/T-CM CAR cells and allowed most pts to receive CAR-T cells within 8 days of apheresis. Dual targeting of CD20 and CD19 with CAR-T cells may improve outcomes in pts with relapsed, refractory MCL.

Obinutuzumab, ibrutinib, and venetoclax were well tolerated and efficacious in relapsed and untreated MCL patients (Le Gouill, Blood 2021). BOVen is a well-tolerated, outpatient regimen associated with high response rates and high rates of undetectable MRD in untreated TP53-mutant MCL. The early PFS and OS estimates with BOVen compare favorably with historical outcomes of chemoimmunotherapy in this high-risk subset of MCL. Based on this data, BOVen emerges as a promising treatment option for TP53-mutant MCL and, therefore, the study was expanded to include an additional 25 (total 50) TP53-mutant MCL patients.

Clinicians are using clonoSEQ to assess MRD across multiple lymphoid malignancies in routine care. In ALL, MRD testing was reported for multiple treatment timepoints whereas in other disease states (CLL, MM, NHL) reported use of the assay was predominantly for monitoring remission. The advent of therapeutic regimens for B-cell malignancies with higher relative response rates denotes the need for sensitive tools that can be used in clinical practice to better assess treatment response and monitor MRD to facilitate future treatment decisions.

All patients were selected from the VRDI Part B (bortezomib, lenalidomide, dexamethasone) consisting of evaluating the preliminary efficacy (complete response [CR] rate) of isatuximab administered at the selected dose in combination with bortezomib based regimen. M-InSight shows accurate monitoring of the depth and kinetics of response to treatment thanks to frequent timepoints. M-InSight can track low level of M-protein in CR patients and detect early relapse.

In patients with AL amyloidosis, the ClonoSEQ assay can identify a sequence consistent with the patient's light or heavy chain isotype almost 80% of the time. Of those cases in which a clonal light chain sequence was consistent with the patient's isotype, the genes identified were from the well described AL-related light chain variable region gene repertoire. These findings indicate that the size of the AL clone does not affect this outcome and suggest that other factors related to the adaptive immune dysregulation of AL or to the multiplex PCR process may be involved.