- |||||||||| MODULE 2: Novel Strategies Combining Bruton Tyrosine Kinase (BTK) and Bcl-2 Inhibitors in CLL (Omni San Diego, Grand Ballroom (Level 2), 4) - Sep 23, 2023 - Abstract #ASH2023ASH_264;
Supported by educational grants from AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, and Lilly. Mechanistic rationale for combining BTK and Bcl-2 inhibitors with or without anti-CD20 antibodies in the management of CLL Long-term efficacy and safety outcomes from early-phase studies evaluating ibrutinib in combination with venetoclax for patients with treatment-na
- |||||||||| Leukeran (chlorambucil) / GSK
Enrollment closed, Enrollment change, Trial primary completion date, Metastases: Chlorambucil in Metastatic PDAC Patients Bearing a Germ Line DNA Defects Repair Mutations (SALE Trial) (clinicaltrials.gov) - Sep 21, 2023
P2, N=20, Active, not recruiting,
Mechanistic rationale for combining BTK and Bcl-2 inhibitors with or without anti-CD20 antibodies in the management of CLL Long-term efficacy and safety outcomes from early-phase studies evaluating ibrutinib in combination with venetoclax for patients with treatment-na Recruiting --> Active, not recruiting | N=30 --> 20 | Trial primary completion date: Jun 2021 --> Jan 2023
- |||||||||| Is Fixed-Duration Therapy the New Standard of Care in Frontline CLL? () - Aug 31, 2023 - Abstract #SOHO2023SOHO_951;
An improved understanding of the disease biology has contributed to the development of novel agents able to target key pathways in CLL.2 Two classes of targeted agents have been extremely impactful in shaping current treatment of CLL: the BCL2 inhibitor venetoclax and the Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib and zanubrutinib...Patients received six 28-day cycles of ibrutinib in combination with fludarabine, cyclophosphamide and rituximab (FCR) followed by 2 years of ibrutinib maintenance...The combination of ibrutinib-venetoclax demonstrated superior progression-free survival (24 months estimated rate 84.4% for patients treated with ibrutinib-venetoclax and 44.1% for patients treated with chlorambucil-obinutuzumab) and superior rates of U-MRD (55.7% vs 21%).15 The time-limited approach with concomitant administration of BTK and BCL2 targeting agents has potential advantages over continuous BTK inhibitor-based therapy in terms of reduced risk for treatment-related side effects due to the prolonged administration and potentially lower costs8 , however, there are still open questions in terms of selection of therapy at time of retreatment and quality and durability of responses to subsequent therapies. It is important to note that treatment with combination of BTKi and venetoclax with or without CD20 monoclonal antibodies is not FDA approved and is still being investigated in clinical trials.
- |||||||||| Covalent Inhibitors of BTK in the Treatment of CLL () - Aug 31, 2023 - Abstract #SOHO2023SOHO_940;
In the frontline setting, the ELEVATE-TN study compared acalabrutinib, either alone or in combination with obinutuzumab, to chlorambucil plus obinutuzumab...Frontline phase 3 trial data comes from the SEQUOIA study, where zanubrutinib was compared with bendamustine plus rituximab...The combination of ibrutinib plus venetoclax has received frontline approval from the EMA. Ongoing studies may offer future options of time-limited therapy involving covalent BTK, but current approaches with indefinite covalent BTK treatment offer a safe and effective strategy to treat CLL patients at this time.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Updates of the Epidemiological Profile and Management of Chronic Lymphocytic Leukemia (Level 3, Hall B3) - Aug 31, 2023 - Abstract #SOHO2023SOHO_845;
CLL patterns included the predominance of urban population from central districts, male gender and patients over 55 years old. RFC regimen proved to be the most efficient in terms of complete response rate and OS.
- |||||||||| Campath (alemtuzumab) / Sanofi, Adcetris (brentuximab vedotin) / Seagen, Takeda, Leukeran (chlorambucil) / GSK
Peripheral cutaneous T-cell lymphoma, NOS: a case report (e-Poster Hall) - Aug 30, 2023 - Abstract #EADV2023EADV_3228;
An individualized approach and risk assessment is still considered the best option for HBV prophylaxis. Given the patient
- |||||||||| Journal, HEOR, Real-world evidence, Real-world: Real-World Evidence on the Clinical Characteristics and Management of Patients with Chronic Lymphocytic Leukemia in Spain Using Natural Language Processing: The SRealCLL Study. (Pubmed Central) - Aug 26, 2023
The most common antineoplastic treatment was ibrutinib in 1L (64.8%) and 2L (62.1%), followed by bendamustine + rituximab (12.6%), obinutuzumab + chlorambucil (5.2%), rituximab + chlorambucil (4.8%), and idelalisib + rituximab (3.9%) in 1L and venetoclax (15.5%), idelalisib + rituximab (6.9%), bendamustine + rituximab (3.5%), and venetoclax + rituximab (3.5%) in 2L. This study expands the information available on patients with CLL in Spain, describing the diversity in patient characteristics and therapeutic approaches in clinical practice.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy. (Pubmed Central) - Aug 16, 2023
These favorable physicochemical properties can effectively facilitate gastrointestinal absorption, blood circulation stability, tumor accumulation, cellular uptake, and cytotoxicity, therefore achieving high oral relative bioavailability (358.72%) and significant tumor growth inhibition while decreasing side effects. Thus, this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.
- |||||||||| Single center report on cohort of patients relapsed on Bruton Tyrosine Kinase inhibitors (BTKi) (Hynes Convention Center Meeting Room 302/304. Level 3 900 Boylston St., Boston, MA) - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_302;
IGHV unmutated status was dominant in BTKi resistant cohort and the most frequently used fragments were different from that of the responsive cohort. Acquired BTK/PLCG2 mutations remained to be key drivers of BTKis resistance but other high-risk factors may affect the outcome of BTKi treatment and the underlying mechanisms should be explored in order to overcome BTKi resistance.
- |||||||||| Anti-Fc?R Antibody Drug Conjugate as a Potential Therapeutic Agent for the Treatment of Chronic Lymphocytic Leukemia () - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_249;
Later developments include chimeric antigen receptor expressing T cells (CAR-T) targeting cell surface proteins (e.g. CD19, ROR1), small molecule inhibitors such as ibrutinib, idelalisib, venetoclax targeting intracellular proteins (e.g. BTK, PI3K?, BCl-2) and combinations thereof have shown excellent clinical activity in patients...Together these experiments demonstrated the specificity and potency of anti-FcuR-ADC in vitro, and studies are underway to evaluate its efficacy in vivo using a patient-derived xengograft CLL model. We envisage that anti-Fc?R-DVD-ADCs may offer a promising modality for the treatment of CLL.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Venetoclax-Obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study () - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_222;
Five years after cessation of Ven-Obi, over half of the patients of this elderly patient population remained in remission, 8% still had uMRD and over 60% had not required second-line treatment. The 1-year Ven-Obi regimen is an effective fixed-duration option for patients with CLL and coexisting conditions.
- |||||||||| Does the Life Expectancy of Elderly CLL Patients Receiving Upfront Targeted Agents Approach the Life Expectancy of the General Population? (Hynes Convention Center Exhibit Hall D, Level 2 900 Boylston St., Boston, MA) - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_115;
Patients enrolled in the CT/CIT arms received chlorambucil (C) as a single agent (14.3%), Bendamustine-Rituximab (BR, 19.6%), C-obinutuzumab (CO, 66%)...Nonetheless, the results of this analysis evaluating the upfront administration of TAs on OS suggest these agents have substantially mitigated but not fully eliminated the shorter OS of CLL patients relative to the AGMGP. Continued development of novel treatment approaches to improve outcome for patients with CLL is needed.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Photocaging of Carboxylic Function Bearing Biomolecules by New Thiazole Derived Fluorophore. (Pubmed Central) - Aug 2, 2023
Furthermore, the thiazole C5-methyl group was easily modified into specific functional groups (CH2Br and CH2OH) for the formation of a series of photocourier molecules containing model compounds (benzoic acids), as well as prodrugs, including salicylic acid, caffeic acid, and chlorambucil via a "benzyl" linker...The fluorophore structure provided stability to the carbocation through the delocalization of the positive charge via resonance structures. Viability assessment of Vero cells using the MTT-test confirmed the weak cytotoxicity of prodrugs without irradiation and it increase upon UV-light.
- |||||||||| Managing Concurrent Gastric Adenocarcinoma and Marginal Zone Lymphoma in an Immigrant Patient Without Access to Insurance (Exhibit Hall) - Jul 29, 2023 - Abstract #ACG2023ACG_4717;
Case Description/ 54-year-old male with Stage IVB MZL status-post Rituximab, Vincristine, and Leukeran, presented with 2-week history of significant bouts of bloody diarrhea and general malaise...Five cycles of the Oxaliplatin /Capecitabine regimen were initiated...The latter delayed the approval of Pembrolizumab (a novel therapy for MSI-H positive GA) and Zanubrutinib (a novel BTK inhibitor for refractory MZL)...Hence, more guidance is needed to navigate therapeutics in concurrent malignancies. It is essential to streamline the process for authorizations for chemotherapeutics, especially for the more vulnerable populations which are prone to getting lost to follow-up, causing poorer outcomes.
- |||||||||| War and the fragility of anticancer drug supply networks in Ukraine () - Jul 27, 2023 - Abstract #ESMO2023ESMO_3203;
10 (32%) were limited per 9-12: ibrutinib, mercaptopurine, eltrombopag, erythropoietin, thrombopoietin, ruxolitinib, venetoclax, brentuximab, gemtuzumab, obinutuzumab...Conclusions Shortages of essential anticancer drugs are a continued challenge in Ukraine during the war. Results are limited by small sample size and limited sampling from regions affected by active hostilities.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Design, synthesis and anticancer evaluation of novel oncolytic peptide-chlorambucil conjugates. (Pubmed Central) - Jul 10, 2023
However, due to the high reactivity of nitrogen mustard, most NMs react with proteins and phospholipids within the cell membrane...Herein, the chlorambucil (CLB, a kind of NM) hybrids were first designed by conjugation with membranolytic peptide LTX-315...Moreover, FXY-3 showed superior in vivo anticancer efficiency in the mouse cancer model. Collectively, this study established an effective strategy to increase the anticancer activity and the nuclear accumulation of NMs, which will provide a valuable reference for future nucleus-targeting modification of nitrogen mustards.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Fecal acute phase proteins in cats with chronic enteropathies. (Pubmed Central) - Jul 4, 2023
Fecal AGP concentration shows promise to differentiate cats with SCGL from cats with IBD and FRE. Fecal ceruloplasmin concentrations may be useful to objectively monitor response to treatment in cats with CE.
- |||||||||| Leukeran (chlorambucil) / GSK
Review, Journal: Management of Waldenstr (Pubmed Central) - Jul 3, 2023
Prospective studies in resource-limited regions are required to further evaluate these essential aspects of the disease. In this document, we issue recommendations based on our local reality.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal. (Pubmed Central) - Jun 30, 2023
While small series have shown no influence on the outcome for treatment with the anti-CD20 antibody rituximab (R) or treatment with cladribine (2-CdA), conflicting data have been reported for alkylating agents, especially chlorambucil and the combination of R?+?chlorambucil. None of other genetic changes seen in MALT lymphoma to date has discernible value in routine clinical applications, but recent data suggest that changes in TNFAIP3(A20), KMTD2 and CARD11 might be associated with response to Bruton kinase inhibitors.
- |||||||||| Leukeran (chlorambucil) / GSK
Preclinical, Journal: In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues. (Pubmed Central) - Jun 30, 2023
Most of the tested compounds showed good inhibitory activity compared with the reference ligand (chlorambucil)...The HOMO and LUMO band gap energies, and the molecular electrostatic potential surface were also deducted for the stable structure of each compound. Also, we studied the prediction of absorption, distribution, metabolism and excretion (ADME) of the compounds.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, Imbruvica (ibrutinib) / AbbVie, J&J
Journal, HEOR, Combination therapy, Cost-effectiveness, Cost effectiveness: Cost-effectiveness analysis of different combination therapies for the treatment of chronic lymphocytic leukaemia in India. (Pubmed Central) - Jun 29, 2023
At the current market prices, regimen comprising of CP as first-line followed by BR as second-line therapy is the most cost-effective strategy for CLL treatment in India. Department of Health Research, Government of India.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Treatment Options for Marginal Zone Lymphoma (LEVEL 3, GENERAL ASSEMBLY) - Jun 21, 2023 - Abstract #SOHO2023SOHO_203;
Bendamustine and chlorambucil are commonly used chemotherapy agents.13 A large, randomized study has shown that the combination of chlorambucil and rituximab is more effective than either chlorambucil or rituximab monotherapy.14 The choice of chemotherapy agents should consider patient age, fitness, and organ functions, as older/frail adults receiving bendamustinerituximab have shown higher rates of fatal toxicities. More intensive doxorubicin-containing combination regimens such as R-CHOP are active but more toxic and should be limited to patients with histological transformation or bulky masses...Second- and subsequent lines of treatment may include rituximab single agent, particularly after durable first remission, and chemotherapy or lenalidomide plus rituximab.15
- |||||||||| 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
- |||||||||| MODULE 3: Chronic Lymphocytic Leukemia (CLL) (Hilton Chicago; Grand Ballroom (Level 2)) - May 26, 2023 - Abstract #ASCO2023ASCO_7062;
This activity is supported by educational grants from AbbVie Inc, Genentech, a member of the Roche Group, Genmab US Inc, Karyopharm Therapeutics, Lilly, Regeneron Pharmaceuticals Inc, Sanofi, and Seagen Inc. Clinical, biological and practical factors in the selection of first-line treatment for CLL requiring active therapyLong-term findings from Phase III studies assessing ibrutinib-, acalabrutinib- and zanubrutinib-based therapy for treatment-na
- |||||||||| Journal, HEOR, IO biomarker, Cost-effectiveness, Cost effectiveness: Cost-effectiveness of targeted treatment vs chemoimmunotherapy in treatment-na (Pubmed Central) - May 15, 2023
Overall, patients with treatment-naive CLL treated with A or A?+?O experienced significant gains in Q-TWiST compared with C?+?O. Several targeted treatments, such as venetoclax + obinutuzumab (VenO) and ibrutinib, have emerged to treat treatment-na
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