- |||||||||| [VIRTUAL] Optimal Frontline Therapy for Young or Fit Patients with Chronic Lymphocytic Leukemia: A Case-Based Discussion () - Sep 6, 2021 - Abstract #SOHO2021SOHO_365;
P2, P3
With the introduction of targeted kinase inhibitors, such as ibrutinib [Bruton’s tyrosine kinase inhibitor (BTKi)], acalabrutinib (BTKi), and venetoclax [B-cell lymphoma-2 inhibitor (BCL2i)], this recommendation has evolved over the last decade to incorporate the use of these agents in this population...The CLL8 Study firmly established FCR as the standard for frontline CLL therapy in young patients.3,4 The benefit of this regimen was more pronounced in patients with mutated IGHV with a 67% rate of 5-year progression-free survival (PFS), compared with 33% in the un-mutated IGHV group.4 Long-term follow-up of the M.D. Anderson frontline FCR study further supported these findings with 54% versus 9% progressionfree at 13 years in the IGHV-mutated and un-mutated groups, respectively.5 The CLL10 Study compared frontline CLL therapy with FCR versus bendamustine plus rituximab (BR).6 Similar to prior FCR frontline studies, patients with IGHV-mutated disease had prolonged 4-year PFS of 65% compared with 25% in the IGHV un-mutated population.6 Overall, FCR was associated with more toxicity but led to prolonged PFS compared with BR, which retained FCR as the standard of care for younger CLL patients.6 After the introduction of ibrutinib, the E1912 Study was launched to understand if the combination of ibrutinib (given continuously) and rituximab (IR) could result in superior clinical outcomes compared with FCR (6 cycles) in the frontline therapy of young CLL patients.7 Overall, IR resulted in prolonged PFS and overall survival (OS) when compared with FCR, making IR one of the standards of care for this population...Another study, A041202, was run concurrently for older adults with CLL and found no significant difference in PFS when comparing ibrutinib with or without rituximab.8 Acalabrutinib, a second-generation and more selective BTKi, with or without the anti-CD20 monoclonal antibody obinutuzumab, was studied as frontline CLL therapy in older adults.9 In patients with mutated IGHV 24-month PFS rates were excellent at 96% and ~80% in those receiving acalabrutinib with and without obinutuzumab, respectively.9 However, no difference in OS has yet been seen between the two arms, so it is unclear if adding obinutuzumab to acalabrutinib has a clinically meaningful outcome...In 12 patients with TP53 mutation or del(17p) in the pivotal study using single-agent acalabrutinib in treatment-naïve patients, the estimated 4-year PFS of this high-risk population was 82%.12 Zanubrutinib was studied specifically in 109 treatment-naïve patients with del(17p).13 Eighteen-month PFS was promising at 89%, but longer follow-up of the study and approval for marketing in CLL are currently pending for this drug...For high- or low-risk patients that desire time-limited therapy, but to avoid toxicity of standard chemoimmunotherapy regimens, the combination of V-O is a good option. Novel approaches in the frontline treatment of CLL aim to build upon the success of targeted agents in frontline CLL treatment through combination of these agents or using them earlier in the course of disease with a goal of deep and prolonged remissions.
- |||||||||| [VIRTUAL] Case Presentation – Frontline Treatment of Older Patient with CLL: Options and Consideration () - Sep 6, 2021 - Abstract #SOHO2021SOHO_362;
Similarly, the ELEVATE-TN study with acalabrutinib ± obinutuzumab in the treatment-naïve older patient population demonstrated continued PFS benefit with the BTKiarms compared to chlorambucil-obinutuzumab leading to its approval in this setting.8 Currently BTKitherapy (± monoclonal antibody) requires indefinite inhibition and continuous therapy...Similarly, the ALPINE study noted reduced rates of atrial fibrillation/fl utter but also a superior objective response rate at an interim analysis in their study of zanubrutinib versus ibrutinib in relapsed/refractory CLL patients.10 Further long-term follow-up will be necessary to confirm if these early differences hold up with time...In addition, there was a higher complete response frequency and higher percentage of patients that were negative for minimal residual disease in both the peripheral blood and bone marrow for the venetoclax–obinutuzumab group than in the chlorambucil–obinutuzumab group...Similarly, the converse is true about a patient with poor renal function and/or inability for close follow-up and management of tumor lysis syndrome due to inadequate social support, and thus therapy with a BTKiwould be chosen. Older patients without any significant comorbidities to preclude any treatment options certainly have more fl exibility based on their desire for continuous versus a time-limited therapy and can take into consideration the timing and duration of therapy as well as the potential toxicities of these therapies.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Review, Journal: Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. (Pubmed Central) - Aug 28, 2021
Notable adverse events such as grade 3 or 4 neutropenia can be managed with supportive therapy and venetoclax dose modifications. In conclusion, fixed-duration venetoclax + obinutuzumab represents an important chemotherapy-free first-line treatment option for patients with CLL, particularly those who are not fit enough to receive intensive chemoimmunotherapy.
- |||||||||| Revlimid (lenalidomide) / BMS, Arzerra (ofatumumab) / Novartis, Genmab
Clinical, Review, Journal: Novel Targeted Therapies for Chronic Lymphocytic Leukemia in Elderly Patients: A Systematic Review. (Pubmed Central) - Aug 27, 2021
Agents like B-cell receptor (BCR) inhibitors (Bruton's tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Trial completion date, Trial primary completion date, Combination therapy: GAZAI: Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma (clinicaltrials.gov) - Aug 26, 2021
P2, N=93, Recruiting,
Trial completion date: Dec 2022 --> Dec 2023 Trial completion date: Sep 2023 --> May 2024 | Trial primary completion date: Jun 2021 --> Nov 2021
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Enrollment open: A Study to Evaluate the Efficacy and Safety of Obinutuzumab, Ibrutinib, and Venetoclax in Patients With Richter's Syndrome; (clinicaltrials.gov) - Aug 25, 2021
P2, N=15, Recruiting,
Initiation date: Jun 2021 --> Nov 2021 Not yet recruiting --> Recruiting
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Trial completion date, Trial primary completion date: CLL2-BAAG: Sequential Regimen of Bendamustin-Debulking Followed by Obinutuzumab, Acalabrutinib and Venetoclax in Patients With Relapsed/Refractory CLL (clinicaltrials.gov) - Aug 24, 2021
P2, N=46, Active, not recruiting,
Not yet recruiting --> Recruiting Trial completion date: Sep 2023 --> Nov 2024 | Trial primary completion date: May 2021 --> May 2023
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Enrollment closed, Minimal residual disease: NEXT STEP: CLL Induction Treatment With Venetoclax and Ibrutinib, Followed by Ibrutinib and Obinutuzumab in Patients With MRD. (clinicaltrials.gov) - Aug 22, 2021
P2, N=85, Active, not recruiting,
Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Trial primary completion date, Combination therapy: SAKK 35/15: Obinutuzumab in Combination With Venetoclax in Previously Untreated Follicular Lymphoma Patients (clinicaltrials.gov) - Aug 18, 2021
P1, N=25, Active, not recruiting,
Despite its limitations, this study describes a new adverse event and identifies a specific subgroup of patients whose clinical management at the time of the infusion of G may need to be refined. Trial primary completion date: Jun 2021 --> Dec 2021
- |||||||||| cibisatamab (RG7802) / Roche, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, RG7827 / Roche
Trial completion date, Trial initiation date, Trial primary completion date, Combination therapy, Metastases: Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment (clinicaltrials.gov) - Aug 18, 2021
P1/2, N=80, Recruiting,
Trial primary completion date: Jun 2021 --> Dec 2021 Trial completion date: Jun 2024 --> Oct 2024 | Initiation date: Apr 2021 --> Jul 2021 | Trial primary completion date: Jun 2024 --> Oct 2024
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Trial completion date, Trial primary completion date: Lenalidomide and Obinutuzumab in Treating Patients With Relapsed Indolent Non-Hodgkin Lymphoma (clinicaltrials.gov) - Aug 18, 2021
P1/2, N=78, Active, not recruiting,
Trial completion date: Jun 2024 --> Oct 2024 | Initiation date: Apr 2021 --> Jul 2021 | Trial primary completion date: Jun 2024 --> Oct 2024 Trial completion date: May 2021 --> May 2022 | Trial primary completion date: May 2021 --> May 2022
- |||||||||| FT596 / Fate Therap
Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Monotherapy: FT596 as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies (clinicaltrials.gov) - Aug 18, 2021
P1, N=285, Recruiting,
Trial completion date: May 2021 --> May 2022 | Trial primary completion date: May 2021 --> May 2022 N=123 --> 285 | Trial completion date: Apr 2037 --> May 2039 | Trial primary completion date: Apr 2022 --> May 2024
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Enrollment open: Venetoclax-Obinutuzumab +/- Acalabrutinib in R/R CLL (clinicaltrials.gov) - Aug 16, 2021
P2, N=40, Recruiting,
N=123 --> 285 | Trial completion date: Apr 2037 --> May 2039 | Trial primary completion date: Apr 2022 --> May 2024 Not yet recruiting --> Recruiting
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Journal: Single-nucleotide Fcγ receptor polymorphisms do not impact obinutuzumab/rituximab outcome in patients with lymphoma. (Pubmed Central) - Aug 12, 2021
P3
FCGR2B was associated with poorer PFS in multivariate analyses comparing T232T with I232I in rituximab- but not obinutuzumab-treated patients with DLBCL (HR, 4.40; 95% CI, 1.71-11.32; P = .002; multiple-test-adjusted P = .03); however, this genotype was rare (n = 13). This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
Enrollment closed, Trial completion date, Trial primary completion date, Metastases: A Phase 1 Study of Acalabrutinib in Japanese Adult Patients With Advanced B-cell Malignancies (clinicaltrials.gov) - Aug 11, 2021
P1, N=35, Active, not recruiting,
High FcγRIIB/FCGR2B expression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP. Recruiting --> Active, not recruiting | Trial completion date: Jul 2023 --> Oct 2022 | Trial primary completion date: Jul 2023 --> Oct 2022
- |||||||||| Darzalex IV (daratumumab) / J&J
Journal: Development of anti-CD32b antibodies with enhanced Fc function for the treatment of B and plasma cell malignancies. (Pubmed Central) - Aug 8, 2021
To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed...In addition, NVS32b CDRs block the CD32b Fc-binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab...Finally, the activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed using samples from B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) patients. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32b+ malignant cells.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, P3 data, Review, Journal: Phase III Clinical Trials in First-Line Follicular Lymphoma: A Review of Their Design and Interpretation. (Pubmed Central) - Aug 7, 2021
However, there are limitations to using PFS as the primary endpoint. Other potential endpoints, including TTNT, progression of disease within 2 years, response rate, and minimal residual disease status are explored.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen
Clinical, Journal, HEOR: Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. (Pubmed Central) - Aug 6, 2021
Obinutuzumab (GA101; G) is a new treatment for follicular lymphoma (FL) that is anticipated to have greater efficacy than the current treatment, rituximab (R)...For estimating costs adapted in the model, FL patients treated with R were identified from Japanese hospital-based claims database and classified into three treatment regimen groups according to chemotherapies used with R: CHOP, CVP, and bendamustine (B)...Differences in the direct medical costs among treatment regimen groups were mostly due to hospitalization costs. This is probably because many Japanese hematologists choose inpatient treatments over outpatient treatments in CHOP-based induction therapy.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Calquence (acalabrutinib) / AstraZeneca
Enrollment open: Avo In R/R And Previously Untreated MCL (clinicaltrials.gov) - Aug 5, 2021
P1/2, N=41, Recruiting,
This is probably because many Japanese hematologists choose inpatient treatments over outpatient treatments in CHOP-based induction therapy. Not yet recruiting --> Recruiting
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen
Clinical, P2 data, Journal: Obinutuzumab and miniCHOP for unfit patients with diffuse large B-cell lymphoma. A phase II study by Fondazione Italiana Linfomi. (Pubmed Central) - Jul 30, 2021
Based on the observed CR rate, study accrual was interrupted due to the very low probability of demonstrating the initial study hypothesis that Ga101-miniCHOP could improve results of historical data obtained with R-miniCHOP in this group of patients. Nonetheless, results achieved with the 33 treated patients confirm activity and good tolerability of the Ga101-miniCHOP regimen for older unfit adult patients with DLBCL.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen
New P2 trial: Obinutuzumab in Primary FSGS (clinicaltrials.gov) - Jul 30, 2021
P2, N=12, Not yet recruiting,
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Review, Journal: Early Relapse in First-Line Follicular Lymphoma: A Review of the Clinical Implications and Available Mitigation and Management Strategies. (Pubmed Central) - Jul 29, 2021
Beyond standard therapy, autologous stem cell transplant and emerging treatment modalities, such as bispecific antibodies and chimeric antigen receptor T-cells, may have a role in future management. Until standard treatments are defined, mitigating the risk of early relapse with effective up-front treatment remains the priority.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Enrollment closed, Phase classification, Enrollment change, Trial completion date, Trial primary completion date, Metastases: GABe2016: First Line Therapy of Advanced Stage Follicular Lymphoma in Patients < 60 Years Not Eligible fo Standard Immunochemotherapy and in All Patients ? 60 Years (clinicaltrials.gov) - Jul 29, 2021
P2, N=46, Active, not recruiting,
Until standard treatments are defined, mitigating the risk of early relapse with effective up-front treatment remains the priority. Recruiting --> Active, not recruiting | Phase classification: P3 --> P2 | N=470 --> 46 | Trial completion date: Jan 2027 --> Nov 2022 | Trial primary completion date: May 2022 --> Nov 2021
- |||||||||| ST-067 / Simcha Therap, Keytruda (pembrolizumab) / Merck (MSD), Gazyva (obinutuzumab) / Roche, Biogen
Enrollment open, Combination therapy, Monotherapy, Metastases: KEYNOTE-E64: Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067 (clinicaltrials.gov) - Jul 29, 2021
P1a, N=198, Recruiting,
Recruiting --> Active, not recruiting | Phase classification: P3 --> P2 | N=470 --> 46 | Trial completion date: Jan 2027 --> Nov 2022 | Trial primary completion date: May 2022 --> Nov 2021 Not yet recruiting --> Recruiting
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen
P2 data, Journal, Residual disease: A fixed-duration, measurable residual disease-guided approach in CLL: follow-up data from the phase 2 ICLL-07 FILO trial. (Pubmed Central) - Jul 24, 2021
P2
No new treatment-related or serious adverse event occurred beyond end of treatment. Thus, in previously untreated, medically-fit patients with CLL, a fixed-duration (15 months), MRD-guided approach achieved high survival rates, a persistent MRD benefit beyond the end of treatment, and low long-term toxicity.
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
Journal: An update on acalabrutinib to treat chronic lymphocytic leukemia. (Pubmed Central) - Jul 24, 2021
Acalabrutinib is approved as monotherapy in the R/R or TN setting, and in the TN setting can be combined with the anti-CD20 monoclonal antibody obinutuzumab. The data for acalabrutinib development and clinical use are discussed in this review.
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