DLBCL: cd79-adc + rituximab = 57% ORR
Foll Lym: =70% ORR
Up to 49% discontinuation due to AEs, mostly peripheral neuropathy, but reversible upon trmt cessation.
Adcetris RCHOP for DLBCL
high-risk DLBCL patients, complete response (CR) rate for RCHOP alone was 26%
Adcetris +R-CHOP = 92% ORR, 58% CR
Adcetris for mycoses fungoides: 70%ORR
In many cases, MMs pretend not be impressed with good news, and upward move is often delayed by a week or two. Or it may be possible that MMs take a while to confer with consultants.
529 DLT of neutropenia can be controlled with steroids and GCSF and new DLT has not been reached with the new protocol, yet efficacy is already seen at 1mg/kg.
Ninety-three percent of patients (14/15) achieved a negative PET scan after 2 cycles . All patients with disease bulk were PET-2 negative (10/10). Ninety-two percent of patients achieved a negative PET scan after 4 cycles of therapy.
The study treatment has been well-tolerated. No pulmonary toxicity has been observed. Serious adverse events have been documented in two patients: febrile neutropenia and grade 3 hypertension. One patient discontinued protocol treatment due to the development of grade 3 peripheral neuropathy after one treatment with BV+AVD.
The overall response rate (ORR) is 78%; including 1 stringent complete response, 2 complete responses, 10 very good partial responses, and 15 partial responses. Two patients achieved a minor response and 6 patients disease stabilization, resulting in a clinical benefit in 100% of the evaluable patients. The ORR was 83% among the 30 evaluable patients receiving the RPTD. Interestingly, the ORR was 70% among the 23 patients with prior exposure to Len and bortezomib, and among 10 patients refractory to prior treatment with Len.
I got the impression that thrombocytopenia will differ with the sequences of the antibody linked to DM1. It could therefore be specific to T-DM1.
thrombocytopenia was observed in 4.7% (7) to 12.9% (6) of patients in phase III studies.
Here's the impt part though: T-DM1 has been generally well tolerated with a lower incidence of grade ≥3 adverse events compared with trastuzumab plus docetaxel (46.4% vs. 90.9%) (5) and lapatinib plus capecitabine (40.8% vs. 57.0%). Other hematologic lineages appear to be relatively unaffected by T-DM1, with low rates of severe anemia, leukopenia, and neutropenia. Some patients do exhibit a slow drift downward in platelet counts with repeated cycles of T-DM1, resembling the pattern induced by cumulative myelosuppression seen with other cytotoxic agents (9). However, even in those patients with a slow downward shift in platelet levels over subsequent cycles,
platelet counts tend to stabilize at a level less severe than grade 3 thrombocytopenia .
Drug-induced thrombocytopenia is relatively common and has been described for hundreds of agents.
However, if compared with Herceptin + Pertuzumab...then it will be another story.
Cynomolgus monkeys dosed with a therapeutic monoclonal antibody (mAbY.1) at ≥50 mg/kg had unexpected acute thrombocytopenia... The hematologic effects made mAbY.1 an unsuitable candidate for further development as a therapeutic agent. This example demonstrates that nonclinical safety studies may be essential for understanding off-target effects of mAbs prior to clinical trials.
Thrombocytopenia, sometimes with other cytopenias, occurs at higher incidence with administration of some therapeutic interferons (IFN), interleukins (IL), and hematopoietic growth factors (e.g., IFNγ, IL-21, IL-3, IL-18, macrophage colony stimulating factor [M-CSF], granulocyte-macrophage colony stimulating factor [GM-CSF.
Which IMGN drug are you guys talking about?
I think they call it profit taking. Sometimes they also call it rotation. I prefer to use the word "manipulation" though.
I was hoping the upward trend will continue until ASH before they start dumping. They'll probably continue dumping until options expiration next week, before they start with a new upward manipulation again until ASH.
Are you invested in any stem cell company for T1D? Which one has the most promising technology of late?
Have you tried the Mannkind dispenser yet? Is it really more convenient or also a pain?
It was just the timing of the release of the ASH abstracts.
It is also ACHN's way of broadcasting to the world that they are experts in structure-based drug design, and they are also able to branch out into other lucrative indications with their in-house expertise.