Hematology - DC

Question 1

ECHELON-1 (Hodgkin’s Disease) - NEJM 2018

Answer 1

P: Stage III/IV HD
I: Brentuximab (anti-CD30 antibody) vedotin + AVD x 6 cycles
C: ABVD x 6 cycles
O: mPFS (primary), OS (secondary). mPFS includes escalation of chemotherapy or addition of radiation as a failure event.

1st analysis of mPFS: 2-year mPFS 82% versus 77% in favour of BV-AVD.

OS update (NEJM): OS benefit (HR 0.60) for BV-AVD compared to ABVD.

Bottom line: BV-AVD improves PFS and OS compared to ABVD in patients with Stage III/IV HD.

Question 2

ZUMA-7 (DLBCL) - NEJM 2022

Answer 2

P: Early (<12 months) relapsed or refractory large B-cell lymphoma
I: axicabtagene ciloleucel (axi-cel)
C: 3 cycles of chemoimmunotherapy followed by autoHSCT in responders
O: mEFS not reached versus 2.3 months in favour of CAR-T. HR 0.35.

Note: 5-year OS data also reported - mOS NR versus 31.1 months in SOC group. Estimated 4-year OS 54.6% versus 46.0% in favour of axicell, HR 0.73 p-value 0.03.

Bottom line: axi-cell improves OS compared to SOC salvage chemotherapy +/- auto-HSCT in early relapsing/refractory DLBCL.

Question 3

TRANSFORM (DLBCL) - Lancet 2022

Answer 3

P: Early (<12 months) relapsed or refractory large B-cell lymphoma
I: Lisocabtagene maraleucel (liso-cel)
C: 2-3 cycles of chemoimmunotherapy followed by autoHSCT in responders
O: EFS by BICR (primary) 41% versus 16% in favour of CAR-T. HR 0.40.

Note: 5-year OS data also reported - mOS NR versus 31.1 months in SOC group. Estimated 4-year OS 54.6% versus 46.0% in favour of axicell, HR 0.73 p-value 0.03.

Bottom line: axi-cell improves OS compared to SOC salvage chemotherapy +/- auto-HSCT in early relapsing/refractory DLBCL.

Question 4

POLARIX (DLBCL) - NEJM 2022

Answer 4

P: Previously untreated intermediate- or high-risk DLBCL (IPI 2-5) without CNS involvement.
I: Polatuzumab vedotin (anti-CD79b antibody linked to MMAE) - R-CHP (Pola-R-CHP) x 6 cycles + 2 cycles of R
C: R-CHOP x6 cycles + 2 cycles R.
O: PFS (secondary outcomes OS and safety). 2-year PFS 76.7% vs 70.2% in favour of Pola-R-CHP. No difference in OS.

Bottom line: Pola-R-CHP improves 2-year progression-free, but not overall, survival in patients with intermediate- or high-risk DLBCL.

Question 5

GHSG HD10 (Hodgkin’s Disease) - JCO 2017

Answer 5

P: Early-stage favourable-risk HD
I/C: 4 arms: 2 cycles ABVD + 20 Gy involved-field radiation, 2 cycles of ABVD + 30 Gy IFRT, 4 cycles ABVD + 20 Gy IFRT, 4 cycles ABVD + 30 Gy IFRT.
O: Freedom for treatment failure (initial 2010 publication), long-term survival data reported 2017. 10-year PFS and OS identical between ABVD x2 + 20 Gy IFRT and ABVD x4 + 30 Gy IFRT.

Bottom line: in early-stage, favourable-risk HD, 2 cycles ABVD + 20 Gy IFRT is non-inferior to 4 cycles ABVD + 30 Gy IFRT.

Question 6

RATHL (Hodgkin’s Disease) - NEJM 2016

Answer 6

P: Stage II - IV HD (40% were Stage II)
I/C: 2 cycles ABVD followed by PET scan.
If negative: 4 more cycles of ABVD or AVD x 4 cycles (bleomycin omitted).
If positive: Escapated BEACOPP or BEACOPP-14.
O: 3-year PFS (non-inferiority) between groups. No difference in PFS or OS between AVD and ABVD in PET-negative group. In PFS-positive group, escalated BEACOPP improved PFS but not OS.

Bottom line: In PET2-negative patients with advanced HD, bleomycin can be dropped for the remaining 4 cycles of chemotherapy.

Note: Stage III/IV patients should be treated with 6 cycles BV-AVD instead as it improves OS compared to 6 cycles of ABVD (ECHELON-1).