Ofatumumab Doesn't Help After Rituximab Fails in Follicular Lymphoma
By John Gever, Senior Editor, MedPage Today
Published: December 09, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Earn CME/CE credit
for reading medical news
Action Points
Explain to interested patients that ofatumumab is not approved for follicular lymphoma, but is approved as second-line treatment for chronic lymphocytic leukemia.
Explain that patients in the study had very poor prognosis and had already failed to respond to a similar drug, so a strong response to ofatumumab would not have been expected.
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
NEW ORLEANS -- Ofatumumab (Arzerra) monotherapy is not a viable treatment option in patients with follicular lymphoma that doesn't respond to rituximab (Rituxan), a researcher said here.
In 116 patients who failed to achieve at least a partial response to rituximab -- either alone or with chemotherapy -- objective responses occurred in only 11% of those taking ofatumumab, reported Anton Hagenbeek, MD, of Academic Medical Center in Amsterdam.
"If we are realistic, there is no role for this antibody as monotherapy in treatment of rituximab-refractory patients" with follicular lymphoma, Hagenbeek told attendees here at the American Society of Hematology's annual meeting.
But he noted that the response was higher -- 22% -- in a subgroup of patients who had failed rituximab monotherapy.
That opens the possibility that ofatumumab might still be helpful in a combination regimen, and studies of such approaches are underway, he said.
Ofatumumab, like rituximab, depletes B cells carrying the CD20 protein, but it is a fully human antibody that has appeared to be more effective than rituximab in certain applications.
An earlier study led by Hagenbeek had found that ofatumumab monotherapy had some activity in patients with relapsed or refractory follicular lymphoma, although only a fraction of the patients had received rituximab.
In the current study, patients were considered refractory to rituximab if they had received at least four infusions without demonstrating at least a partial response.
To qualify, patients were not permitted to have received allogeneic stem cell transplants ever or autologous transplants within the previous six months.
The group had follicular lymphoma of grade 1 or 2 by WHO criteria and ECOG performance status of zero to 2.
Twenty-seven patients had received rituximab as monotherapy; 45 had received the drug as part of a combination regimen, while 44 failed on the drug when it was given as maintenance after chemotherapy (which may or may not have included rituximab).
Two open-label doses of ofatumumab were used, 500 mg or 1,000 mg weekly, with up to eight infusions. Median follow-up was 4.7 months.
The dosage appeared to have no effect on objective response rates, which were 13% for the lower dose and 10% for the higher dose.
Only one patient had a complete response, on the 1,000-mg dose.
About 30% of patients on the lower dose and half of those taking the higher dose had stable disease.
Median progression-free survival time was six months, Hagenbeek reported.
Patients who had failed rituximab in combination with chemotherapy -- either as maintenance or as part of an induction regimen -- had much worse responses to ofatumumab monotherapy, with objective response rates of 7% to 9%, compared with 22% of those who failed rituximab monotherapy.
Hagenbeek noted that patients in the study had very poor prognosis to begin with. The median number of prior regimens was four, and two-thirds of cases were considered refractory to chemotherapy.
Hagenbeek ofatumumab was relatively well tolerated. Slightly more than half of patients had reactions to the first infusion, but each subsequent infusion led to reactions in fewer than 20% of patients.
Grade 3-4 nonhematologic adverse events were rare, with one case of serious urticaria, two infections, and two with cough.
Some 15% of patients had neutropenia and 10% had leukopenia.
Because of the signs of activity seen in this study -- albeit limited -- several additional studies are now underway to examine ofatumumab in other approaches to follicular lymphoma.
One phase II study is investigating the drug combined with chemotherapy in rituximab-refractory patients, Hagenbeek said.
Three other trials are testing ofatumumab in follicular lymphoma believed to be sensitive to rituximab. One is a phase II study of ofatumumab monotherapy, and another combines it with chemotherapy.
The third is a phase III, head-to-head comparison of ofatumumab and rituximab in untreated or relapsed patients, Hagenbeek said.
The study was funded by Genmab and GlaxoSmithKline.
Hagenbeek reported relationships with Roche, Bayer, and Genmab. Other co-authors had relationships with these firms and with GlaxoSmithKline, Novartis, Bristol-Myers Squibb. Some co-authors were employees of GlaxoSmithKline and Genmab.
By John Gever, Senior Editor, MedPage Today
Published: December 09, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Earn CME/CE credit
for reading medical news
Action Points
Explain to interested patients that ofatumumab is not approved for follicular lymphoma, but is approved as second-line treatment for chronic lymphocytic leukemia.
Explain that patients in the study had very poor prognosis and had already failed to respond to a similar drug, so a strong response to ofatumumab would not have been expected.
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
NEW ORLEANS -- Ofatumumab (Arzerra) monotherapy is not a viable treatment option in patients with follicular lymphoma that doesn't respond to rituximab (Rituxan), a researcher said here.
In 116 patients who failed to achieve at least a partial response to rituximab -- either alone or with chemotherapy -- objective responses occurred in only 11% of those taking ofatumumab, reported Anton Hagenbeek, MD, of Academic Medical Center in Amsterdam.
"If we are realistic, there is no role for this antibody as monotherapy in treatment of rituximab-refractory patients" with follicular lymphoma, Hagenbeek told attendees here at the American Society of Hematology's annual meeting.
But he noted that the response was higher -- 22% -- in a subgroup of patients who had failed rituximab monotherapy.
That opens the possibility that ofatumumab might still be helpful in a combination regimen, and studies of such approaches are underway, he said.
Ofatumumab, like rituximab, depletes B cells carrying the CD20 protein, but it is a fully human antibody that has appeared to be more effective than rituximab in certain applications.
An earlier study led by Hagenbeek had found that ofatumumab monotherapy had some activity in patients with relapsed or refractory follicular lymphoma, although only a fraction of the patients had received rituximab.
In the current study, patients were considered refractory to rituximab if they had received at least four infusions without demonstrating at least a partial response.
To qualify, patients were not permitted to have received allogeneic stem cell transplants ever or autologous transplants within the previous six months.
The group had follicular lymphoma of grade 1 or 2 by WHO criteria and ECOG performance status of zero to 2.
Twenty-seven patients had received rituximab as monotherapy; 45 had received the drug as part of a combination regimen, while 44 failed on the drug when it was given as maintenance after chemotherapy (which may or may not have included rituximab).
Two open-label doses of ofatumumab were used, 500 mg or 1,000 mg weekly, with up to eight infusions. Median follow-up was 4.7 months.
The dosage appeared to have no effect on objective response rates, which were 13% for the lower dose and 10% for the higher dose.
Only one patient had a complete response, on the 1,000-mg dose.
About 30% of patients on the lower dose and half of those taking the higher dose had stable disease.
Median progression-free survival time was six months, Hagenbeek reported.
Patients who had failed rituximab in combination with chemotherapy -- either as maintenance or as part of an induction regimen -- had much worse responses to ofatumumab monotherapy, with objective response rates of 7% to 9%, compared with 22% of those who failed rituximab monotherapy.
Hagenbeek noted that patients in the study had very poor prognosis to begin with. The median number of prior regimens was four, and two-thirds of cases were considered refractory to chemotherapy.
Hagenbeek ofatumumab was relatively well tolerated. Slightly more than half of patients had reactions to the first infusion, but each subsequent infusion led to reactions in fewer than 20% of patients.
Grade 3-4 nonhematologic adverse events were rare, with one case of serious urticaria, two infections, and two with cough.
Some 15% of patients had neutropenia and 10% had leukopenia.
Because of the signs of activity seen in this study -- albeit limited -- several additional studies are now underway to examine ofatumumab in other approaches to follicular lymphoma.
One phase II study is investigating the drug combined with chemotherapy in rituximab-refractory patients, Hagenbeek said.
Three other trials are testing ofatumumab in follicular lymphoma believed to be sensitive to rituximab. One is a phase II study of ofatumumab monotherapy, and another combines it with chemotherapy.
The third is a phase III, head-to-head comparison of ofatumumab and rituximab in untreated or relapsed patients, Hagenbeek said.
The study was funded by Genmab and GlaxoSmithKline.
Hagenbeek reported relationships with Roche, Bayer, and Genmab. Other co-authors had relationships with these firms and with GlaxoSmithKline, Novartis, Bristol-Myers Squibb. Some co-authors were employees of GlaxoSmithKline and Genmab.
tjaaa der er jo ikke noget nyt i det. Men man har svært ved at forstå hvorfor Lisa synes det her var særligt spændende. Der er jo på ingen måde grund til at tro at man efter en sådan fremlæggelse vil lave en ansøgning i NHL baseret på det refrac forsøg....så vi skal jo igang med de head to head forsøg som også er markedets forventning.
Så der er jo ikke noget nyt i det, men det blev da ikke bedre af denne præsentation.
Så der er jo ikke noget nyt i det, men det blev da ikke bedre af denne præsentation.
Det er i givet fald det samme søm, som allerede er blevet banket i Genmab mange gange i løbet af efteråret. Men det kan da godt være, at det skal bankes i en gang til på grund af stemningen.
For mig at se intet afgørende nyt bortset fra nogle mindre detaljer. Lisa havde jo antydet noget nyt på ASH, så på den baggrund måske svagt skuffende, men basalt set er det 4 måneder gammelt nyt. Og Lisas nyhed kan jo vedrøre noget andet (??).
Ofatumumab er ikke en super fantastisk mirakelkur for verdens allermest syge i denne gruppe af patienter, men der er intet, der tyder på, at det er et dårligere produkt end Rituximab og det tåles godt af patienterne.
For mig at se intet afgørende nyt bortset fra nogle mindre detaljer. Lisa havde jo antydet noget nyt på ASH, så på den baggrund måske svagt skuffende, men basalt set er det 4 måneder gammelt nyt. Og Lisas nyhed kan jo vedrøre noget andet (??).
Ofatumumab er ikke en super fantastisk mirakelkur for verdens allermest syge i denne gruppe af patienter, men der er intet, der tyder på, at det er et dårligere produkt end Rituximab og det tåles godt af patienterne.
9/12 2009 22:01 Sibelius 0
23288 Det virker som en dyr og defensiv måde Genmab angriber disse forsøg på. Hvorfor er det egentlig at man laver langvarige og dyre forsøg hvor man tester på patienter der er på gravens rand og ikke har effekt af konkurrenternes midler (alene eller i kombination med kemo o.l). Som med Azerra giver det jo i bedste fald mulighed for at blive valgt når alt andet er fejlet og så forlade sig på off label salg.
Er der nogen af Genmab specialisterne der kan forklare det?
Er der nogen af Genmab specialisterne der kan forklare det?
Ja det er et godt spørgsmål.
Svaret er at man har relativt større chance at blive godkendt i en indikation hvor der ikke er andre behandlingsmuligheder. Så det er en afvejning mellem at man kan få rigtigt dårlige resultater, men samtidigt er kravene til resultaterne ikke så høje, hvis der er tale om et unmet medical need. Dette var ihvertfald rationalet for Genmab i CLL.
I NHL var strategien nok den at det var en genvej til at få Arzerra meget tidligt ud i et flertal af indikationer. Nu må de så gå den lange vej med head to head studier etc. Havde NHL refrac braget igennem, så havde det nok skåret 1-2 år af time to market i NHL og det er jo værd at tage med.
Det kiksede, men rationalet fejler ikke noget.
Hvad der derimod fejler noget er at Genmab måde at kommunikere med markedet på, så analytikerne havde slet ikke forstået indikationen og kom med udsagn om at det skulle give 35-45% Orr. 10% var simpelthen et kæmpe chok.
Svaret er at man har relativt større chance at blive godkendt i en indikation hvor der ikke er andre behandlingsmuligheder. Så det er en afvejning mellem at man kan få rigtigt dårlige resultater, men samtidigt er kravene til resultaterne ikke så høje, hvis der er tale om et unmet medical need. Dette var ihvertfald rationalet for Genmab i CLL.
I NHL var strategien nok den at det var en genvej til at få Arzerra meget tidligt ud i et flertal af indikationer. Nu må de så gå den lange vej med head to head studier etc. Havde NHL refrac braget igennem, så havde det nok skåret 1-2 år af time to market i NHL og det er jo værd at tage med.
Det kiksede, men rationalet fejler ikke noget.
Hvad der derimod fejler noget er at Genmab måde at kommunikere med markedet på, så analytikerne havde slet ikke forstået indikationen og kom med udsagn om at det skulle give 35-45% Orr. 10% var simpelthen et kæmpe chok.
Hmmmm.... det ser unægteligt ud til at Ofatumumab og Genmab kun kan levere dårlige nyheder PT.
Omvendt ser det ud for TopoTarget, der mere og mere fremstår som DKs nye lokomotiv på kræftområdet.
Jeg glæder mig til den dag, hvor du Aka, - og Troldmand, Solsen m.fl. begynder at interessere jer lige så meget for kometen TopoTarget, som I har gjort det i Genmab og Neurosearch.
Det ville få TopoTargets åbentlyse potentiale frem i lyset, og ydermere aflaste de stakkels svenskere, der næsten alene kæmper for en seriøs debat om aktien.
Et (igangsætter)link til en desværre alt for kort TopoTarget investorpræsentation (så er bolden givet op):
http://webcast.zoomvision.se/denmark/clients/daf/daf_topotarget_090916/
Omvendt ser det ud for TopoTarget, der mere og mere fremstår som DKs nye lokomotiv på kræftområdet.
Jeg glæder mig til den dag, hvor du Aka, - og Troldmand, Solsen m.fl. begynder at interessere jer lige så meget for kometen TopoTarget, som I har gjort det i Genmab og Neurosearch.
Det ville få TopoTargets åbentlyse potentiale frem i lyset, og ydermere aflaste de stakkels svenskere, der næsten alene kæmper for en seriøs debat om aktien.
Et (igangsætter)link til en desværre alt for kort TopoTarget investorpræsentation (så er bolden givet op):
http://webcast.zoomvision.se/denmark/clients/daf/daf_topotarget_090916/
9/12 2009 20:52 gentogen 023284 Blot til orientering så er der en tråd længere nede om Topo (som dog ikke rigtig er blevet en tråd endnu). I nævnte tråd refereres til nogle resultater fra 2 studier. Responsrater på 14 (vel ikke voldsomt imponerende) og 32 (ser bedre ud).
Det undrer mig i øvrigt lidt, at der i disse Topo studier gøres en del ud af "stabil sygdom" (tallene 14 og 32 er dog uden). Hvis man regner det med, så er ovenfor diskuterede Genmab studie også en stor succes.
Men tak for tip.
Det undrer mig i øvrigt lidt, at der i disse Topo studier gøres en del ud af "stabil sygdom" (tallene 14 og 32 er dog uden). Hvis man regner det med, så er ovenfor diskuterede Genmab studie også en stor succes.
Men tak for tip.
Man kan kun sammenligne studiers succesrate indenfor samme indikation (PTCL) - alt andet ville være at sammenligne æbler og pærer. Topo's studier er interessante, da der ikke er godkendte behandlinger i indikationerne (PTCL og CTCL), derudover er Belinostat interessant pga. sin lave toxitet, hvilket betyder at det vil være stærkt brugbart i kombinationsbehandlinger.
Man kan evt få det i light version i webcastet
http://webcast.zoomvision.se/denmark/clients/daf/daf_topotarget_090916/frameset.php?chapter_1.asx&&9&video
Man kan evt få det i light version i webcastet
http://webcast.zoomvision.se/denmark/clients/daf/daf_topotarget_090916/frameset.php?chapter_1.asx&&9&video
9/12 2009 22:53 csinvest 023294 Warrant-prgm Genmab 09122009
http://www.finansnyheder.dk/News/ShowNewsstory.aspx?StoryID=10781628
http://www.finansnyheder.dk/News/ShowNewsstory.aspx?StoryID=10781628
10/12 2009 11:51 gentogen 023306 Jeg var sådan set heller ikke ude på overhovedet at gøre mig klog på Topo eller på at sammenligne, men jeg har bare undret mig over, at der i Genmabs tilfælde af alle analytikere og kommentatorer er blevet set totalt bort fra en ellers MEGET høj "stabil sygdom" procent, som jeg nemlig selv ved offentliggørelsen af Genmab studiet var tilbøjelig til at udlægge lidt positivt, hvilket ingen andre imidlertid har gjort, så jeg har egentlig gået og taget til efterretning, at den slags data åbenbart er totalt uinteressante. Umiddelbart ville jeg ellers mene, at stabil sygdom i Genmabs tilfælde (og Topos for den sags skyld) burde være en slags indirekte bevis på produktets virkning. Så mit lile indlæg var egentlig mest tænkt som en slags spørgsmål til, hvad man kan og skal lægge i data for "stabil sygdom" i al almindelighed.
10/12 2009 12:04 faurschou 023307 Uden at være sikker så tror jeg at stabil sygdom først og fremmest tillægges betydning, når der er tale om kandidater til områder, der ikke har en godkendt behandling. (det er jo altid godt at kunne tilbyde noget i stedet for intet - derfor fast track og "lavere succeskriterier").
Og jeg beklager min dårlige læsning af dit indlæg, trætheden havde vist vundet i går aftes.
Og jeg beklager min dårlige læsning af dit indlæg, trætheden havde vist vundet i går aftes.
