How exactly do American doctors treat CLL?

Back to the ASH abstracts. This is one that tries to work out what is actually hapenning in America with the treament of CLL.

2864 Patterns of Care for Patients with Chronic Lymphocytic Leukemia (CLL): The Connect® CLL Disease Registry Jeff Sharman, Christopher R Flowers, Mark Weiss, David Grinblatt, Charles Farber, Neil Kay, Thomas Kipps, Nicole Lamanna, Chris Pashos, Ian W Flinn, Mark Kozloff, Susan Lerner, Arlene Swern, Kristen A Sullivan, Thomas K. Street, and Michael Keating.

Introduction:

Clinical trials have illuminated a number of unique treatment strategies for patients with CLL. The impact of these strategies on routine practice remains unknown as trial participants may not reflect the same population encountered outside of a clinical trial setting. Many questions remain regarding the sequencing of therapies based on age and performance status. By characterizing current patterns of care; patients, treating physicians, and regulatory agencies will be able to understand the current landscape of CLL treatment. The Connect® CLL registry was designed to report the natural history and real world management of patients receiving therapy for CLL. In this first report, we characterize the therapeutic approaches used for the treatment of patients with CLL of different age groups (i.e. < 65 years, 65–75 years, and ≥ 75 years) and with an ECOG PS status score of 0 compared to 1 or greater.

Methods:

Connect® CLL is a prospective, longitudinal, observational, multi-center registry conducted in community and academic research centers in the United States. At present, 237 sites are actively participating with a projected study enrollment of 1500 patients. Eligible patients are to be enrolled within 2 months of being initiated on any line of therapy; whether initial therapy or salvage therapy. Each patient will be followed for up to 60 months. Clinical data, physician choices, patient-reported health-related quality of life, response and survival are to be collected approximately every 3 months during participation.

Results:

A total of 607 patients have been enrolled (4% from academic sites) with a median age of 70 years. 198 were < 65 years old (age group 1), 187 were between 65–75 years old (age group 2), and 222 were ≥ 75 years old (age group 3). ECOG status varied across the three age groups, with an ECOG status score of ≥ 1 for 39%, 52%, and 70% of patients respectively. Treatment patterns varied across the age groups and by ECOG status in the 496 patients reporting therapies. The most commonly recorded first-line regimens independent of age included fludarabine (F) cyclophosphamide (C) and rituximab (R) (33%), bendamustine (B) +/- R (19%), F +/- R (15%), or investigational therapy (15%). For second-line regimens and beyond, the most frequently recorded regimen was B +/- R (30%), FCR (23%), other F-based regimens (13%), or investigational therapy (8%).

Note that nearly three quarters of patients over-75 had a poor ECOG score. This is why you can't translate clinical trials results to how to treat most cases of CLL. The average age of diagnosis in CLL is at least 70 and the age thay theu need treatment for the first time is even older.


The use of FCR for first-line treatment decreased significantly with increasing age group, (45%, 32%, 20%, for age group 1, 2, 3 respectively, p=0.04, spearman correlation) while use of F +/- R remained level across the age groups (14%, 15%, 15%, respectively). Compared to age group 1, first-line therapy with B +/- R in age groups 2 and 3 (15%, 22%, 21%, respectively) was higher but did not achieve statistical significance. B +/- R represented the most common treatment for all age groups (37%, 26%, 29%, respectively) as second line therapy but did not vary by age (P=0.35). The use of chlorambucil was infrequent in all age groups, but was more common in age group 3 patients compared to the others (P=0.01), in both first-line (2%, 4%, 12%, respectively) and subsequent lines of therapy (0%, 1%, 8%, respectively).

Note: only 35% of the over-75s even had fludarabine, let alone FCR. Mind you this would have included many mutated patients who would never need any treatment.

Treatment assignments did not vary by ECOG PS score for patients in age group 1. First-line therapy for patients with an ECOG PS score of 0 in age groups 2 and 3 consisted of FCR (32% and 15%, respectively), F +/- R (19% and 15%, respectively), B +/- R (16% and 15%, respectively), and alkylating agents (3% and 23%, respectively). Patients in age groups 2 and 3 with ECOG PS score ≥ 1 received B +/- R regimen (33% and 22%, respectively), FCR (23% and 21%, respectively), F +/- R (14% and 10%, respectively) and alkylating agents (7% and 9%, respectively) as first-line therapy. Further description and clarification on the various treatment regimens based on the three age groups and by ECOG PS score will be presented at the meeting.

Note: B +/- R does not have any validation by clinical trials in this situation. It is toxic, but I am willing to believe that there is another mechanism by which it has an advantage second line.

Conclusion:

The Connect® CLL Registry is the largest prospective, multicenter registry in the United States evaluating management for patients with CLL. With the currently available data, we characterize the extent to which age and performance status are associated with treatment selection in both first-line and subsequent lines of therapy in routine practice. As enrollment increases and additional follow-up is completed, the data will provide more extensive and real world overview of the current treatment strategies used in CLL patients.

This study is obviously funded by Celgene. I wonder what their ulterior motive is in doing so.