Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia (Italian Cooperative Study Group on Chronic Myeloid Leukemia)
Phase 3N = 322
- Population
- Previously untreated or minimally treated Philadelphia chromosome-positive CML.
- Design
- Prospective randomized comparison, 1986 to 1988, designed with 80 percent power to detect a 20 percent difference in median survival; interferon alfa-2a versus conventional chemotherapy (hydroxyurea or busulfan).
- Arms
- Conventional chemotherapy (control, n = 104): Hydroxyurea or busulfan
- Interferon alfa-2a (experimental, n = 218): Recombinant interferon alfa-2a
- People
- Tura S, Italian Cooperative Study Group on Chronic Myeloid Leukemia
Δ median OS+20 monthsΔ 72-month OS+21 pointsΔ Karyotypic response+25 pointsΔ median OS+40 monthsΔ 120-month OS+17 pointsΔ median OS+23 months
Show the numbers
| Endpoint | Analysis | Interferon alfa-2a | Conventional chemotherapy | Effect |
|---|---|---|---|---|
| OSRandomized patients (322) | primaryItalian 1994 | median 72 months; 50% at 6 y | median 52 months; 29% at 6 y | P=0.002The abstract states P = 0.002 for both the time-to-progression and survival comparisons. It also reports time to progression to accelerated or blastic phase as a median of more than 72 months with interferon alfa-2a versus 45 months with conventional chemotherapy (P<0.001); see the TTP result. |
| TTPRandomized patients (322) | primaryItalian 1994 | — | median 45 months | P<0.001Published median time to progression was more than 72 months with interferon alfa-2a (a lower bound, so not entered as a number) versus 45 months with conventional chemotherapy. Only the chemotherapy arm can be entered, so this result must not be plotted or compared as a pair. |
| Karyotypic responseRandomized patients (322)More than 33 percent of metaphases negative for the Philadelphia chromosome. | primaryItalian 1994 | 30% | 5% | P<0.001 |
| OSLow-risk patients; intention-to-treat analysis (stated in the 1998 abstract) with patients who had allogeneic transplant in chronic phase censored at transplant | long term-updateItalian 1998 | median 104 months (85–127); 47% at 10 y (36–59%) | median 64 months (49–98); 30% at 10 y (16–44%) | P=.03Risk grouping is as used in the long-term paper; the abstract does not define it beyond mentioning Sokal risk as associated with survival. |
| OSNon-low-risk patients; intention-to-treat analysis (stated in the 1998 abstract) with patients who had allogeneic transplant in chronic phase censored at transplant | long term-updateItalian 1998 | median 69 months (56–76); 16% at 10 y (8–24%) | median 46 months (39–61); 5% at 10 y (0–11%) | P=.006 |
| Endpoint | Analysis | Interferon alfa-2a | Conventional chemotherapy | Effect |
|---|---|---|---|---|
| OSRandomized patients (322) | primaryItalian 1994 | median 72 months; 50% at 6 y | median 52 months; 29% at 6 y | P=0.002The abstract states P = 0.002 for both the time-to-progression and survival comparisons. It also reports time to progression to accelerated or blastic phase as a median of more than 72 months with interferon alfa-2a versus 45 months with conventional chemotherapy (P<0.001); see the TTP result. |
| TTPRandomized patients (322) | primaryItalian 1994 | — | median 45 months | P<0.001Published median time to progression was more than 72 months with interferon alfa-2a (a lower bound, so not entered as a number) versus 45 months with conventional chemotherapy. Only the chemotherapy arm can be entered, so this result must not be plotted or compared as a pair. |
| Karyotypic responseRandomized patients (322)More than 33 percent of metaphases negative for the Philadelphia chromosome. | primaryItalian 1994 | 30% | 5% | P<0.001 |
| OSLow-risk patients; intention-to-treat analysis (stated in the 1998 abstract) with patients who had allogeneic transplant in chronic phase censored at transplant | long term-updateItalian 1998 | median 104 months (85–127); 47% at 10 y (36–59%) | median 64 months (49–98); 30% at 10 y (16–44%) | P=.03Risk grouping is as used in the long-term paper; the abstract does not define it beyond mentioning Sokal risk as associated with survival. |
| OSNon-low-risk patients; intention-to-treat analysis (stated in the 1998 abstract) with patients who had allogeneic transplant in chronic phase censored at transplant | long term-updateItalian 1998 | median 69 months (56–76); 16% at 10 y (8–24%) | median 46 months (39–61); 5% at 10 y (0–11%) | P=.006 |
- Conventional chemotherapy (control)
- Interferon alfa-2a (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Conventional chemotherapy | Interferon alfa-2a |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 45 | 54.9% | 64.8% |
| 90 | 30.1% | 42.0% |
| 135 | 16.5% | 27.3% |
| 180 | 9.1% | 17.7% |
- Conventional chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Conventional chemotherapy |
|---|---|
| 0 | 100.0% |
| 28 | 65.0% |
| 56 | 42.2% |
| 84 | 27.4% |
| 113 | 17.5% |
Appears in
Sources
Italian Cooperative Study Group on Chronic Myeloid Leukemia, Tura S, Baccarani M, Zuffa E, Russo D, Fanin R, et al. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994;330(12):820-5.
Italian Cooperative Study Group on Chronic Myeloid Leukemia. Long-term follow-up of the Italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia. Blood. 1998;92(5):1541-8.