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ASCO 2019 | Results of a phase II study: Post-transplant cyclophosphamide in matched and haploidentical transplant recipients receiving myeloablative timed sequential busulfan conditioning regimen
On Saturday, June 1 2019, during the American Society for Clinical Oncology (ASCO) annual meeting in Chicago, US, Uday R. Popat, from The University of Texas MD Anderson Cancer Center, Houston, TX, discussed the results of a prospective phase II study (NCT02861417), evaluating post-transplant cyclophosphamide (PT-Cy) in matched and haploidentical transplant recipients receiving a myeloablative fractionated busulfan conditioning regimen.1
There is an unmet need for a myeloablative conditioning regimen that reduced relapse rates without increasing Graft-versus-Host Disease (GvHD) related non-relapse mortality. Dr. Popat discussed how timed sequential busulfan (TSB) with fludarabine (Flu) is a promising myeloablative regimen for patients undergoing matched sibling (MSD) or unrelated (MUD) donor transplantation (HCT) with low non-relapse mortality (NRM), which has until now not been tested in haploidentical (haplo) donor transplantation.
Patient characteristics
|
|
N = 55 |
Percentage % |
|
Diagnosis |
||
|
AML/MDS |
30 |
55 |
|
CML/MPD |
9 |
16 |
|
Lymphoma |
5 |
9 |
|
Myeloma |
5 |
9 |
|
ALL |
6 |
11 |
|
Age, median (range) |
47 |
15-65 |
|
Comorbidity score > 2 |
22 |
40 |
|
Disease Risk Index |
||
|
High |
18 |
32 |
|
Intermediate |
32 |
58 |
|
Low |
5 |
9 |
|
Donor |
||
|
Matched Related |
11 |
20 |
|
Haploidentical related |
26 |
47 |
|
Matched Unrelated |
18 |
33 |
|
Cell source |
|
|
|
Peripheral blood |
26 |
31 |
|
Bone Marrow |
29 |
35 |
Methods
- Patients received fixed doses of Busulfan (BU) 80mg/m2 either on day -13 and -12 (n=45) or on -20 and -13 (n=10).
- Then, on day -6 to -2 Flu 40mg/m2 plus Bu were administered daily with Bu dosed to achieve target area under the curve (AUC) of 20,000 µmol/min
- Thiotepa 5mg/kg was given on day -7 to recipients of haplo donors
- GvHD prophylaxis:
- PT-Cy 50mg/kg on day 3 and 4
- Tacrolimus +/- mycophenolate mofetil starting day 5
Results (median follow up of 17 months):
|
|
Results (N = 55) |
95% CI |
|
OS, 1 yr. in all patients |
71 % |
(60-84%) |
|
OS, 1 yr. after MSD HCT (n =11) |
91 % |
(75-100 %) |
|
OS, 1 yr. after MUD HCT (n =18) |
72 % |
(54-96 %) |
|
OS, 1 yr. after haplo HCT (n =26) |
62 % |
(45-83%) |
|
PFS, 1 yr. |
63 % |
(51-77 %) |
|
Relapse, 1 yr. |
17 % |
(7-27%) |
|
NRM, 1 year |
20 % |
(9-31 %) |
|
Acute GVHD II-IV |
38 % |
(25-51 %) |
|
Acute GVHD III-IV |
9 % |
(1-17 %) |
|
Chronic GVHD, 1 yr. |
10 % |
(2-18 %) |
|
Extensive Chronic GVHD |
8 % |
(0-15 %) |
|
Graft failure |
0 % |
0 % |
Engraftments and Chimerism
- There was no graft failure
- Neutrophils: 17 (13-39) days
- Platelets: 25 (11-167)
Grade 3-5 Toxicity
|
|
Grade 3 |
Grade 4 |
Grade 5 |
Total (%) |
|
Neutropenic Fever |
32 |
0 |
0 |
32 (58) |
|
Infections |
12 |
1 |
5 |
18 (33) |
|
Mucositis |
13 |
1 |
0 |
14 (25) |
|
Bilirubin |
6 |
1 |
0 |
7 (13) |
|
Pneumonia |
4 |
2 |
0 |
6 (11) |
|
Pulmonary |
1 |
3 |
1 |
5 (9) |
|
VOD |
3 |
0 |
1 |
4 (7) |
|
Hemorrhagic Cystitis |
4 |
0 |
0 |
4 (7) |
*Only ≥ 2 total events per system were considered in the study
Conclusions:
Dr. Popat concluded that myeloablative fractioned busulfan conditioning combined with PT-Cy GvHD prophylaxis seems to reduce both, the incidence of severe acute and chronic GvHD and relapse rate in the haplo HCT setting and needs to be studied further.
References