CLL/SLL Flashcards

Question

What are some of the S/e of Ibrutinib:

Answer 1

Diarrhea Peripheral edema Dry eye Arthralgia Nausea Vomiting Hypertension (14%, 4% severe) AFIb 6% Increased risk of bleeding (Severe in 6%) Liver dysfunction

Answer 2

Phase III trial, 800 older adults, prev untreated CLL 3 arms: 1) Chlorambucil 2) Chlorambucil + Rituximab 3) Chlorambucil + Obinutuzumab RESULTS: 1) CR\>C - ORR 70% vs 30% - CR 8% vs 0% - higher rate of G3/4 neutropenia 25% vs 15% - similar rates of infection 10% - Improved PFS 16m vs 11m - \* NO OS BENEFIT 2) OC\>C - even higher CR rates - improved PFS 27m vs 11m - improved OS HR 0.41 3) RC

Answer 3

COMPLEMENT 1 trial Phase III 450 adults previously untreated CLL not eligible for Fludarabine-based therapy. 2 arms: 1) Ofatumumab+Chlorambucil 2) Chlorambucil Up to 12 cycles Results: - higher ORR 80% vs 70% (C) - CR 14% vs 1% - median duration of response 22m vs 13m - PFS 22 vs 13m - 2y survival ~ 90%; 3y survival ~85%

Answer 4

Infusion reaction - 10% severe Neutropenia Weakness Headache Leukopenia Herpes simplex LRTI Arthralgia Upper abdominal pain Progressive Multifocal leukoencephalopathy Pre-medication required: - acetaminophen - glucocorticoid - antihistamine

Answer 5

Premedications required. #1 consist of 2 doses - 300mg D1, - 1/52 later 1000mg D8 Subsequent cycles: - single dose 1000mg D1 Q28days until best response for a minimum of 3# and maximum of 12#

Answer 6

Generally used for older adults who are not candidates for: - Ibrutinib - Combination of Chlorambucil + anti-CD20 monoclonal Ab 1) Phases 3 trial - 200 adults, ECOG 2 or better - symptomatic, treatment naive CLL - 2arms: Chlorambucil vs Fludarabine RESULTS: - ORR 50% (C) vs 70% - CR 0% (C) vs 7% - ~rates of PFS 18m (C) vs 19m - non significant trend towards improved OS 60m vs 50m - lower rats of G3/4myelotoxicity 20% vs 40% - similar rates of infections 30%

Answer 7

1) Pulsed intermittent dose schedule - eg. Single oral dose 0.8mg/kg Q4w 2) Chlorambucil 0.5mg/kg D1 D15 q28days for six cycles

Answer 8

Anemia Neutropenia Thrombocytopenia Infertility Seizures Hepatotoxic it Hypersensitivity Drug fever Pulmonary fibrosis Interstitial pneumonia

Answer 9

1) Clinical trial 2) Ibtrutinib 3) Fludarabine combinations --\> Ibrutinib 4) non-myeloablative allogenic HCT for younger patients with a matched related or matched unrelated donor.

Answer 10

An open-label, phase III randomized trial compared six courses of FCR with six courses of FC in 817 previously untreated patients with CLL. FCR resulted in the following significant findings: ●Higher rates of overall (95 versus 88 percent) and complete (44 versus 22 percent) response ●Longer median progression-free survival (52 versus 33 months) ●Better overall survival at three years (87 versus 83 percent) ●Higher rates of severe (grade 3/4) neutropenia (34 versus 21 percent), leukocytopenia (24 versus 12 percent) ●Similar rates of severe (grade 3/4) infections (25 versus 21 percent) ●Similar rates of treatment-related deaths (2 versus 3 percent)

Answer 11

For most younger patients, we suggest the use of fludarabine-based therapies rather than more recently approved agents, such as bendamustine (Grade 2C). Specifically, we use combination therapy with either fludarabine plus rituximab (FR) or fludarabine, cyclophosphamide, and rituximab (FCR) * FR results in overall response and CR rates of approximately 90 and 47 percent, respectively. The administration of FR to patients with CLL can be complicated by infusion-related reactions and tumor lysis syndrome. Several variations on dose and schedule have been used. * FCR results in overall response and CR rates of approximately 90 to 95 and 40 to 70 percent, respectively. CR achieved with FCR appears to be "deeper" with frequent cases demonstrating no detectable disease on flow cytometry. The FCR regimen has been administered in different variations. * Bendamustine has demonstrated superior response rates when compared with chlorambucil in prospective, randomized trials. No survival benefits have been noted and bendamustine has not been compared directly with fludarabine-based therapy.

Answer 12

The iwCLL defines "active disease" by the presence of one or more of the following criteria: Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly. Massive nodes (ie, at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. Progressive lymphocytosis with an increase of more than 50 percent over a two-month period or LDT of less than six months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of two weeks over an observation period of two to three months. In patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/L), LDT should not be used as a single parameter to define a treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infection) should be excluded. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy. Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: a. Unintentional weight loss of 10 percent or more within the previous six months b. Significant fatigue (ie, ECOG PS 2 or worse; inability to work or perform usual activities) c. Fevers higher than 100.5°F or 38.0°C for two or more weeks without other evidence of infection d. Night sweats for more than one month without evidence of infection