A Descriptive Analysis of Obinutuzumab Usage in a Single Canadian Centre
Bibliographic record
Abstract
Abstract Background:Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in North America with the majority of patients being over the age of 70 (Goede et al, 2014). CLL is a heterogeneous disease with some patients undergoing treatment at time of diagnosis, while others follow along a more indolent, asymptomatic course. When indicated, the choice of treatment is based on the patient's functional status, renal function and other comorbidities (Shanafelt, 2013). Previous studies have shown that unfit patients treated with Obinutuzumab plus Chlorambucil have shown prolongation of progression free survival and higher rates of complete response compared to other monoclonal based regimens (Goede et al, 2014). The aim of this study is to investigate the clinical use and uptake of Obinutuzumab in combination with Chlorambucil in a Canadian based population. Methods:All patients receiving Obinutuzumab were identified using the CLL CAISIS database. Then a retrospective chart review was conducted for patients approved for first-line antibody treatment with Obinutuzumab from January 1, 2014 to December 31, 2017. Data including patient characteristics, patterns of treatment, reported toxicities, response rates and survival data were collected and analyzed. This data was used to determine the overall safety and efficacy of this treatment regimen. Results: There were a total of 66 patients that met the inclusion criteria for this study. This cohort consisted of 54.5% males and 45.5% females, with a median age at diagnosis of 68 years (range: 46-94). Within this population 47 patients underwent florescence in situ hybridization testing, which identified 32 patients with chromosomal abnormalities. The immunoglobulin heavy chain variable region gene mutation was also tested in 41 patients, and identified 22 patients that were unmutated. At the time of treatment the median age was 73 (range: 55-98) with a median Cumulative Illness Rating Scale (CIRS) score of 8 (range: 3-15). Of the 66 patients who started treatment with Obinutuzumab, 50 patients (76%) achieved a partial response and 5 patients (8%) had no response. Of note, 21 patients (31.8%) discontinued treatment prior to completion of all six cycles due to cytopenias (4), other comorbidities (4), progression of CLL (2), decline in functional/mental status (2), patient request (2) and other (7). In regards to their treatment there was a high incidence of infusion related reactions (IRRs) on the first day of treatment, with 30 patients (45.5%) requiring intervention. There was a subset of 15 patients that had received low dose Chlorambucil prior to treatment with Obinutuzumab which resulted in a lower average lymphocyte count (38.1) and lower rate of IRRs (33%) compared to those with no prior Chlorambucil (average lymphocyte count: 66.5, rate of IRR: 42%). Due to toxicity and tolerability of Chlorambucil, dose reduction was observed in 37 patients (56%) throughout all six cycles of treatment. In the end, only 18 patients (27.3%) received all doses of Obinutuzumab and Chlorambucil while 37 patients (56%) received all doses of Obinutuzumab. Within the entire cohort, 12 patients have relapsed and 9 of these patients have required additional therapy. This relapse rate can be attributed to lack of response to Obinutuzumab (3), a 17p del (1), poor prognostic markers (5), and inadequate Obinutuzumab (1). Conclusion:In this current study, our results demonstrate that the majority of patients in this cohort were able to complete treatment with Obinutuzumab. Although our demographics were similar to previous studies, we found higher partial response rates (76%) likely due to differences in standards of practice, such as imaging studies after treatment. Disclosures Whiteside: Roche: Membership on an entity's Board of Directors or advisory committees, Other: teaching sessions. Dawe:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees. Johnston:Roche: Other: unrestricted grant received in the past; Abbvie: Other: unrestricted grant received in the past; Teva: Other: unrestricted grant received in the past; Gilead: Other: unrestricted grant received in the past; Janssen: Other: unrestricted grant received in the past. Banerji:Roche: Other: Unrestricted grant received in the past; Janssen: Other: Unrestricted grant received in the past; Abbvie: Other: Unrestricted grant received in the past; Gilead: Other: Unrestricted grant received in the past; Teva: Other: Unrestricted grant received in the past.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.006 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".