Page 219 - 2021_04-Haematologica-web

BV-DHAP in relapsed or refractory Hodgkin lymphoma
AB
Figure 3. Kaplan-Meier exploratory analysis. Kaplan-Meier exploratory analysis for all 55 phase II patients and six patients from phase I who were treated at the same dose level, including the number of patients at risk at 1, 2 and 3 years with regard to (A) progression-free survival (PFS) stratified for patients with a metabolic complete response (mCR; n=48) or partial response (mPR; n=5) on the positron emission tomography-computed tomography (PET-CT) scan after three cycles of BV- DHAP, measured from the time of that PET-CT scan, and (B) PFS stratified for relapsed patients (n=37; defined as recurrent disease after having reached a complete response on first-line treatment) versus patients with primary refractory disease (n=24; no complete response on first-line treatment), measured from enrollment. BV: brentuximab vedotin; DHAP: dexamethasone, high-dose cytarabine, cisplatin.
Table 3. Serious adverse events grade 3 or 4 during brentuximab vedotin and dexamethasone, high-dose cytarabine and cisplatin. Serious adverse event Cycle 1 Cycle 2 Cycle 3 Total**
(n=55) (n=53) (n=51) (n=55)
CTCAEgrade(n) 34343434
Recovered
All
All
With sequela* All
All
All
All
All
All
All
All
Febrileneutropenia Infection
Renal function disorder Sepsis
Epistaxis
Fever
Elevatedliverenzymes Infusion-related reaction Malaise
Nausea/vomiting
Periodic paralysis (hypokalemia) Total
Individualpatients†
Individual patients total‡
5 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 1 0 8 1
7 1
8 (15%)
0 0
1 0
0 0
0 1
1 0
0 0
0 1
1 0
1 0
0 0
0 0
4 2 9 0 19 3
4 2 7 0 15 3
6 (11%) 7 (14%) 18 (33%)
3 0 1 0 2 0 1 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0
8 1 2 0 2 0 1 1 1 0 1 0 0 1 1 0 1 0 1 0 1 0
*Persisting grade 1 or 2 nephrotoxicity (e.g.,decreased glomerular filtration rate or persisting high levels of creatinine).**Patients with a specific toxicity in more than one cycle were only counted once in the column representing the total toxicity. †Total of patients who experienced one or more grade 3 or 4 toxicity during the concerning cycle. ‡Total of patients who experienced one or more grade 3 or 4 toxicity during the concerning cycle. n: number; CTCAE: Common Terminology Criteria for Adverse Events.
An exploratory analysis on PFS showed that patients with an mPR prior to BEAM/auto-PBSCT have a higher risk of relapse, despite conversion to an mCR after auto- PBSCT. This finding is in line with other trials investigating risk factors for relapse after auto-PBSCT.5-7 PET-adapted therapy could probably further improve outcome by inten- sifying treatment for high-risk patients with new agents, such as checkpoint inhibitors in addition to BV. Moreover, a group of patients at low-risk for relapse, might possibly be cured with a combination of new drugs only, without the toxic consequences of HDC and auto-PBSCT. Risk stratification based on the PET-CT scan at relapse could also be further improved by quantitative analysis and the assessment of metabolic tumor volume.41,42
The addition of BV to salvage treatment has not yet been investigated in a randomized phase III trial. However, several phase II studies have now shown that BV in combination with chemotherapy results in high mCR rates prior to HDC/auto-PBSCT. A combined pooled analysis of all of these studies is planned to give more insight into the effect of BV on response rates and toxicity in this setting.
In conclusion, in R/R cHL, three cycles of BV-DHAP is a highly effective salvage regimen resulting in an mCR rate of 81% prior to HDC/auto-PBSCT as shown by independ- ent central PET-CT review. Patients should be monitored closely for toxicity, especially hematologic toxicity, nephrotoxicity and liver toxicity.
haematologica | 2021; 106(4)
1135