Contributions
Abstract: PB1865
Type: Publication Only
Background
VEN can cause rapid tumor debulking in patients (pts) with relapsed/refractory CLL. Current VEN dosing schedule with TLS prophylaxis/monitoring averts overt TLS, but further data on emergent biochemical changes during VEN initiation are needed to guide practice.
Aims
To report on laboratory abnormalities observed during VEN initiation with 5-wk dose ramp up and current TLS prophylaxis/monitoring recommendations.
Methods
Pts were included from phase 2 trials of VEN for CLL with del(17p) (n=51) or prior BCRi therapy (n=117). VEN started at 20 mg QD with ramp up to 400 mg over 5 wk. Pts were categorized as low (L) TLS risk (nodes <5 cm and ALC <25), medium (M; node ≥5 – <10 cm or ALC ≥25), or high (H; node ≥10 cm or ≥5 cm and ALC ≥25). Laboratory values, AEs, and relevant concomitant medications during ramp up were analyzed.
Results
TLS risk was categorized as 36% L, 36% M, and 27% H. 96% of pts completed ramp up; most in 5 wk. TLS AEs were reported in 4 pts (2 M; 2 H), with no clinical TLS and 1 laboratory TLS meeting Howard criteria (HC*).
During VEN ramp up, 114 pts had potassium (K) >upper limit of normal (ULN) (1 K>HC); 21 were treated for rising or sustained K >ULN. 16 of these 21 had pre-VEN initiation K>ULN. 5/21 pts interrupted VEN for 1 day and all restarted VEN.
119 pts had phosphate (P) >ULN. 20 pts received P binder for P>HC during VEN ramp up and all others resolved without additional medication. Most instances were isolated; 4 pts had concurrent calcium (Ca2+) or uric acid (UA) changes, and P was not treated in these cases.
70% of pts received allopurinol and 20% allopurinol and rasburicase at VEN start. 6 pts received rasburicase in addition to ongoing prophylaxis. Though 144 pts had Ca2+ n of pts TLS risk All N=168 L n=61 M n=61 H n=46 K >ULN >6 mmol/L* Treated 41 0 4 40 1 10 33 0 7 114 1 21 P >ULN >1.5 mmol/L* Treated 34 18 1 44 27 8 41 34 11 119 79 20 Ca2+ <0.3 µmol/L* Treated 45 0 0 58 4 3 41 4 3 144 8 6 UA >ULN >476 µmol/L* Treated 3 2 2 4 2 1 6 4 3 13 8 6 *Howard criteria (Howard et al, , N Engl J Med 2011)
Conclusion
Despite the frequency of K >ULN, treatment was applied in 13% of pts for rising or sustained elevation, and most had pre-VEN K >ULN. Most cases of P >ULN were isolated, asymptomatic, and resolved without intervention. VEN causes rapid tumor cytoreduction consistent with analyte changes, though clinical sequelae are rare and mitigated by approved dose ramp up, TLS prophylaxis/monitoring, and timely intervention.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Abstract: PB1865
Type: Publication Only
Background
VEN can cause rapid tumor debulking in patients (pts) with relapsed/refractory CLL. Current VEN dosing schedule with TLS prophylaxis/monitoring averts overt TLS, but further data on emergent biochemical changes during VEN initiation are needed to guide practice.
Aims
To report on laboratory abnormalities observed during VEN initiation with 5-wk dose ramp up and current TLS prophylaxis/monitoring recommendations.
Methods
Pts were included from phase 2 trials of VEN for CLL with del(17p) (n=51) or prior BCRi therapy (n=117). VEN started at 20 mg QD with ramp up to 400 mg over 5 wk. Pts were categorized as low (L) TLS risk (nodes <5 cm and ALC <25), medium (M; node ≥5 – <10 cm or ALC ≥25), or high (H; node ≥10 cm or ≥5 cm and ALC ≥25). Laboratory values, AEs, and relevant concomitant medications during ramp up were analyzed.
Results
TLS risk was categorized as 36% L, 36% M, and 27% H. 96% of pts completed ramp up; most in 5 wk. TLS AEs were reported in 4 pts (2 M; 2 H), with no clinical TLS and 1 laboratory TLS meeting Howard criteria (HC*).
During VEN ramp up, 114 pts had potassium (K) >upper limit of normal (ULN) (1 K>HC); 21 were treated for rising or sustained K >ULN. 16 of these 21 had pre-VEN initiation K>ULN. 5/21 pts interrupted VEN for 1 day and all restarted VEN.
119 pts had phosphate (P) >ULN. 20 pts received P binder for P>HC during VEN ramp up and all others resolved without additional medication. Most instances were isolated; 4 pts had concurrent calcium (Ca2+) or uric acid (UA) changes, and P was not treated in these cases.
70% of pts received allopurinol and 20% allopurinol and rasburicase at VEN start. 6 pts received rasburicase in addition to ongoing prophylaxis. Though 144 pts had Ca2+ n of pts TLS risk All N=168 L n=61 M n=61 H n=46 K >ULN >6 mmol/L* Treated 41 0 4 40 1 10 33 0 7 114 1 21 P >ULN >1.5 mmol/L* Treated 34 18 1 44 27 8 41 34 11 119 79 20 Ca2+ <0.3 µmol/L* Treated 45 0 0 58 4 3 41 4 3 144 8 6 UA >ULN >476 µmol/L* Treated 3 2 2 4 2 1 6 4 3 13 8 6 *Howard criteria (Howard et al, , N Engl J Med 2011)
Conclusion
Despite the frequency of K >ULN, treatment was applied in 13% of pts for rising or sustained elevation, and most had pre-VEN K >ULN. Most cases of P >ULN were isolated, asymptomatic, and resolved without intervention. VEN causes rapid tumor cytoreduction consistent with analyte changes, though clinical sequelae are rare and mitigated by approved dose ramp up, TLS prophylaxis/monitoring, and timely intervention.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical